SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Mutation V617F

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 47 clinical trials

Clinical Trials


1 Efficacy of Tyrosine Kinase Inhibition in Reducing Eosinophilia in Patients With Myeloid and/or Steroid-Refractory Hypereosinophilic Syndrome

The purpose of this study is to evaluate the safety and efficacy of the tyrosine kinase inhibitor, imatinib mesylate (Gleevec ) in reducing peripheral blood eosinophilia in patients with the myeloid form of hypereosinophilic syndrome (HES). Patients with the hypereosinophilic syndrome who meet a set of criteria designed to select patients with the myeloid form of the disease, as well as patients without myeloid disease who are refractory to standard therapy for HES, will be admitted on this protocol. A thorough clinical evaluation will be performed with emphasis on potential sequelae of eosinophil-mediated tissue damage. A baseline bone marrow will be obtained to exclude leukemia or lymphoma and to assess the degree and nature of eosinophilopoiesis. Bone marrow, blood cells and/or serum will also be collected to test for the presence of a recently described mutation that is associated with imatinib-responsiveness in HES, and to provide reagents (such as DNA, RNA, and specific antibodies) and for use in the laboratory to address issues related to the mechanism of action of imatinib mesylate in HES. Imatinib mesylate will be initiated at a dose of 400 mg daily, the FDA-approved dose for the treatment of chronic myelogenous leukemia. In patients who demonstrate a complete clinical and hematologic response to imatinib therapy and who do not have life-threatening disease, the dose will be decreased gradually to 100mg daily and then discontinued. In order to minimize bone marrow suppression, other myelosuppressive agents will be tapered and discontinued during the first week of therapy with imatinib mesylate. Complete blood counts will be performed weekly for the first month and biweekly thereafter. Clinical assessments will be performed every three months to assess progression of end organ damage. In patients who demonstrate a complete clinical and hematologic response to imatinib therapy and who do not have life-threatening disease, the dose will be decreased gradually to 100 mg daily and then discontinued. In the event of clinical, hematologic or molecular relapse during the taper, the imatinib dose will be increased to a maximum of 600 mg daily to achieve a second remission. Laboratory monitoring will be performed as above except for molecular monitoring which will be monitored monthly if drug is discontinued or molecular relapse occurs. Once a stable dosing regimen is achieved for greater than or equal to 6 months in subjects who have undergone dose descalation or greater than or equal to 2 years in subjects receiving 300-400 mg of imatinib daily who did not qualify for dose de-escalation, the frequency of NIH visits and end organ assessments will be decreased to 6 months, with molecular monitoring every 3 months and monthly routine laboratory assessments.

NCT00044304 Hypereosinophilic Syndrome Drug: Imatinib Drug: Ruxolitinib
MeSH: Hypereosinophilic Syndrome Syndrome

abnormal tyrosine kinase (i.e., FIP1L1-PDGFRA, JAK2 V617F). --- V617F ---

Primary Outcomes

Description: The percentage of subjects who reach and eosinophil count in the normal range

Measure: peripheral blood absolute eosinophil count.

Time: one month (for imatinib) and 3 months (for ruxolitinib).

Secondary Outcomes

Description: The % of subjects who reach an eosinophil count in the normal range

Measure: peripheral blood eosinophil count

Time: 3,6,9 and 12 months

Description: The % of subjects who reach an eosinophil count below 1500/mm3

Measure: peripheral blood eosinophil count

Time: 1, 3, 6, 9, and 12 months

Description: The % of subjects who achieve molecular remission on therapy

Measure: abnormal tyrosine kinase (i.e., FIP1L1-PDGFRA, JAK2 V617F)

Time: every 3 months for 5 years

Description: The duration of remission following cessation of therapy

Measure: clinical, hematologic and molecular remission

Time: every 3 months for 5 years

2 Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders

The three main chronic myeloproliferative disorders are polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). These are clonal neoplastic diseases characterized by proliferation of one or more hematopoietic lineages. Recently a mutation of the Janus Kinase 2 (JAK2) gene that leads to the substitution of phenylalanine for valine at position 617 of the JAK2 protein, JAK2 V617F, has been found in 76% to 97% of patients with PV, 29% to 57% of patients with ET and 50% of patients with IMF. This mutation confers constitutive activity on to the JAK2 protein and appears to play an important role in the pathobiology of these conditions. However, not all patients with myeloproliferative disorders have this mutation and it may not be the primary cause of these diseases. The primary goal of this prospective natural history study is to investigate the molecular basis of these diseases in groups of patients who have JAK2 V617F and in those who do not. A second goal is to identify biomarkers for PV and the other myeloproliferative disorders that are easier to measure than JAK2 V617F. Approximately, 150 patients with myeloproliferative disorders will be studied over 3 years. The studies will involve the collection of 40 mL to 50 mL of peripheral blood from each subject. The blood will be used to assess neutrophil gene and protein expression, gene polymorphisms, and plasma protein levels.

NCT00433862 Polycythemia Vera Essential Thrombocytosis Idiopathic Myelofibrosis Neutrophils Chronic Myeloproliferative Disorders
MeSH: Polycythemia Vera Primary Myelofibrosis Polycythemia Myeloproliferative Disorders Thrombocytosis Thrombocythemia, Essential Disease
HPO: Myeloproliferative disorder Polycythemia Thrombocytosis

Recently a mutation of the Janus Kinase 2 (JAK2) gene that leads to the substitution of phenylalanine for valine at position 617 of the JAK2 protein, JAK2 V617F, has been found in 76% to 97% of patients with PV, 29% to 57% of patients with ET and 50% of patients with IMF. --- V617F ---

The primary goal of this prospective natural history study is to investigate the molecular basis of these diseases in groups of patients who have JAK2 V617F and in those who do not. --- V617F ---

A second goal is to identify biomarkers for PV and the other myeloproliferative disorders that are easier to measure than JAK2 V617F. --- V617F ---


3 A Phase 2, Prospective, Randomized, Multicenter, Double-blind, Active-control, Parallel-group Study to Determine the Safety of and to Select a Treatment Regimen of CC-4047 (Pomalidomide) Either as Single-agent or in Combination With Prednisone to Study Further in Subjects With Myelofibrosis With Myeloid Metaplasia

The purpose of this study is to determine the safety of and to select a treatment regimen of pomalidomide (CC-4047) either as single-agent or in combination with prednisone to study further in patients with myelofibrosis with myeloid metaplasia (MMM).

NCT00463385 Myelofibrosis With Myeloid Metaplasia Myeloid Metaplasia Myelofibrosis Drug: Pomalidomide Drug: Prednisone Drug: Placebo to pomalidomide Drug: Placebo to prednisone
MeSH: Primary Myelofibrosis Metaplasia

Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline.. Number of Participants With Adverse Events (AEs). --- V617F ---

Primary Outcomes

Description: A clinical responder was defined as either: A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders.

Measure: Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment

Time: Up to 168 days

Secondary Outcomes

Description: A clinical responder was defined as either: A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders.

Measure: Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment

Time: Up to 336 days

Description: The time to the first clinical response achieved within 168 days after the first study drug dosing date was calculated for participants who achieved a clinical response as: Start date of the first clinical response - the first study drug date +1. A clinical responder was defined as either: A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable.

Measure: Time to the First Clinical Response

Time: Up to 168 days

Description: For RBC-transfusion-dependent patients, duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the date of the first RBC-transfusion administrated at or more than 56 days after the response started. For patients who did not receive a subsequent transfusion after the response started, the end date of response was censored at the day of last hemoglobin assessment. For RBC-transfusion-independent patients, the duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the earlier of the date of a hemoglobin increase of < 2.0 g/dL and the date of a RBC transfusion at ≥ 56 days after the response started. For patients whose hemoglobin measurements were always ≥ 2.0 g/dL and never received a RBC transfusion after response started, the end date of the response was censored at the date of last hemoglobin measurement. Kaplan-Meier methodology was used.

Measure: Duration of First Clinical Response

Time: Up to 40 months

Description: The FACT-An comprises the four subscales of the 27-item FACT-General Scale (FACT-G), Physical Well-being, Social/Family Well-being, Emotion Well-being, Functional Well-Being, and the Additional Concerns Anemia subscale. Questions are rated on a scale from 0 to 4, where higher scores indicate more impact on quality of life. Physical Well-being consists of 7 questions, the subscale score ranges from 0-28; Social/Family Well-being consists of 7 questions, the subscale score ranges from 0-28; Emotion Well-being consists of 6 questions, the subscale score ranges from 0-24; Functional Well-Being consists of 7 questions, the subscale score ranges from 0-28; Anemia subscale consists of 20 questions, the subscale score ranges from 0-80; Total FACT-An score ranges from 0-188.

Measure: Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores

Time: Baseline and Cycle 6 (168 days).

Description: Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment.

Measure: Change From Baseline in Hemoglobin Concentration for Responders

Time: Baseline, Cycle 6 (168 days)

Description: Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment.

Measure: Change From Baseline in Hemoglobin Concentration for Non-Responders

Time: Baseline, Cycle 6 (168 days)

Description: Participants rated abdominal discomfort or pain over the previous week on a scale from zero to ten, where zero is no discomfort or pain and ten is the worst pain imaginable.

Measure: Change From Baseline in Likert Abdominal Pain Scale

Time: Baseline and Cycle 6 (168 days)

Description: Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline.

Measure: Percentage of Participants With Clinical Response by Baseline JAK2 Assessment

Time: Up to 336 days

Description: A serious AE (SAE) was defined as any AE which resulted in death or was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or constituted an important medical event (events that may have jeopardized the patient or required intervention to prevent one of the outcomes listed above). The severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) or according to the following scale: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Death. The Investigator determined the relationship between study drug and the occurrence of an AE as "Not Related" or "Related" (since the study was double-blinded, a patient receiving only prednisone could have an AE that was judged as related to pomalidomide, and vice-versa).

Measure: Number of Participants With Adverse Events (AEs)

Time: From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).

4 An Open-Label Study of Oral CEP-701 in Patients With Polycythemia Vera or Essential Thrombocytosis With the JAK2 V617F Mutation

This is an 18-week open-label, multicenter study to evaluate the efficacy and tolerability of CEP-701 (lestaurtinib) treatment in patients with Polycythemia Vera (PV) and patients with Essential Thrombocytosis (ET).

NCT00586651 Polycythemia Vera Essential Thrombocytosis Drug: lestaurtinib
MeSH: Polycythemia Vera Polycythemia Thrombocytosis Thrombocythemia, Essential
HPO: Polycythemia Thrombocytosis

An Open-Label Study of Oral CEP-701 in Patients With Polycythemia Vera or Essential Thrombocytosis With the JAK2 V617F Mutation. --- V617F ---

Determine whether a specific reduction in the JAK2 V617F allele has been indicated in this study.. null. --- V617F ---

- The patient has a detectable JAK2 V617F mutation. --- V617F ---

Primary Outcomes

Measure: Determine whether a specific reduction in the JAK2 V617F allele has been indicated in this study.

Time: 18 weeks +

Secondary Outcomes

Measure: - improvements in hemoglobin values, neutrophil count, and platelet count. - reduction in dose of hydroxyurea - reduction in splenic enlargement - rate of phlebotomy

Time: 18 weeks +

5 A Phase IIA Study of the Histone-deacetylase Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases

Primary Objective: To evaluate efficacy and safety of ITF2357 in the treatment of patients with JAK2V617F positive myeloproliferative diseases [Polycythemia Vera (PV), Essential Thrombocytosis (ET), Myelofibrosis (MF)]. Efficacy was evaluated by ad hoc haematological and clinical criteria for PV and ET, and by internationally established response criteria (EUMNET criteria) for MF. Safety was evaluated by number of subjects experiencing an Adverse Event (AE), type, frequency, severity, timing and relatedness of AEs, including changes in vital signs and clinical laboratory results. Secondary Objective: To evaluate the JAK2 mutated allele burden by quantitative Real-Time Polymerase Chain Reaction (qRTPCR).

NCT00606307 Myeloproliferative Diseases Drug: ITF2357
MeSH: Myeloproliferative Disorders
HPO: Myeloproliferative disorder

A Phase IIA Study of the Histone-deacetylase Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases. --- V617F ---

Phase IIA Study of the HDAC Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases Primary Objective: To evaluate efficacy and safety of ITF2357 in the treatment of patients with JAK2V617F positive myeloproliferative diseases [Polycythemia Vera (PV), Essential Thrombocytosis (ET), Myelofibrosis (MF)]. --- V617F ---

A serious AE (SAE) is defined as an untoward (unfavourable) medical occurrence that at any dose results in death, or is life-threatening or requires inpatient hospitalisation or prolongation of existing hospitalisation, or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.. Inclusion Criteria: - Signed Informed Consent Form - Male or female, age ≥ 18 years - Confirmed diagnosis of PV/ET/MF according to the revised World Health Organisation criteria - JAK-2 V617F positivity - In need of cytoreductive therapy when hydroxyurea is not indicated (e.g. --- V617F ---

positive serology IgM) - Known HIV infection - Active hepatitis B and/or C infection - History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications - Eastern Cooperative Oncology Group (ECOG) performance status 3 or greater - Platelets count <100x109/L within 14 days before enrolment - Absolute neutrophil count <1.2x109/L within 14 days before enrolment - Percentage of blast cells in peripheral blood >10% within 14 days before enrolment - Serum creatinine >2xULN (Upper limit of normal) - Total serum bilirubin >1.5xULN - Serum AST (aspartate aminotransferase) / ALT (alanine aminotransferase) > 3xULN - Interferon alpha within 14 days before enrolment - Hydroxyurea within 14 days before enrolment - Anagrelide within 7 days before enrolment - Any other investigational drug within 28 days before enrolment Inclusion Criteria: - Signed Informed Consent Form - Male or female, age ≥ 18 years - Confirmed diagnosis of PV/ET/MF according to the revised World Health Organisation criteria - JAK-2 V617F positivity - In need of cytoreductive therapy when hydroxyurea is not indicated (e.g. --- V617F ---

Primary Outcomes

Description: Patients with Objective Response were defined as those patients achieving a complete, major, moderate or minor (only for Myelofibrosis patients) response during the experimental treatment course. The "best response" is reported hereunder by intensity of response.

Measure: Number of Patients With Objective Responses (Complete, Major, Moderate or Minor Responses), in Terms of Best Overall Response

Time: Every single week from week 1 to week 24 of treatment

Secondary Outcomes

Description: This outcome was assessed by quantitative real time Polymerase Chain Reaction (RT PCR). At each time point, the number of patients is the following: Screening: N=29 Week 12: N=20 Week 24: N=18 EOT: N=24. End of treatment corresponds to the last visit performed before treatment discontinuation.

Measure: Change in JAK2 Mutated Allele Burden

Time: At screening, at week 12, at week 24, at the end of treatment (EOT) visit

Description: An adverse event (AE) is any untoward occurrence in a patient or clinical investigation subject administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The adverse events must to be followed to the end of study (28 days after the last study drug intake). A serious AE (SAE) is defined as an untoward (unfavourable) medical occurrence that at any dose results in death, or is life-threatening or requires inpatient hospitalisation or prolongation of existing hospitalisation, or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.

Measure: Number of Subject Experiencing an Adverse Event

Time: At weekly visits (Days 8, 15, 22, 36, 43, 50, 64, 71, 78, 99, 127, 155); At monthly visits (Days 29, 57, 85 113, 141,169); at end of treatment visit

6 A Multicenter, Open Label Phase I/II Study of CEP-701 (Lestaurtinib) in Adults With Myelofibrosis

Myelofibrosis is the gradual replacement of bone marrow (place where most new blood cells are produced) by fibrous tissue which reduces the body's ability to produce new blood cells and results in the development of chronic anemia (low red blood cell count). One of the main distinctions of myelofibrosis is "extramedullary hematopoesis", the migration or traveling of the blood-forming cells out of the bones to other parts of the body, such as the liver or spleen, resulting in an enlarged spleen and liver. Treatment for myelofibrosis is unsatisfactory and there is no medication that is specifically used in the treatment of myelofibrosis. There is a protein that is found to be present in the majority of myelofibrosis patients (JAK2) and the drug Lestaurtinib is being studied to see if it will stop this protein from functioning and thereby help control the disease. This study is divided into two Phases (1 & 2). In phase 1 we will be looking for the dose of study medication (Lestaurtinib) that will be the highest dose a patient can take without experiencing serious side effects, maximum tolerated dose (MTD). In phase 2, after the MTD dose has been established in phase 1, we will be investigating how well CEP-701 (Lestaurtinib) works at suppressing the protein (JAK2). The investigators also wish to find out important biologic characteristics or features of myelofibrosis through an additional correlative biomarker study (MPD-RC #107). The correlative biomarker study is a study that is related to the main study, but is looking to answer different questions than the main study. The purpose of the biomarker study is to understand the causes of MPD and to develop improved methods for the diagnosis and treatment of these diseases, while the main study is trying to find out how well CEP-701 (Lestaurtinib) will work in treating the myeloproliferative disease.

NCT00668421 Myelofibrosis Essential Thrombocythemia Polycythemia Vera Drug: CEP-701 (Lestaurtinib)
MeSH: Polycythemia Vera Primary Myelofibrosis Polycythemia Thrombocytosis Thrombocythemia, Essential
HPO: Polycythemia Thrombocytosis

To estimate the efficacy of a novel kinase inhibitor in subjects with myelofibrosis, as determined by a reduction in JAK2 V617F allele frequency in peripheral blood neutrophils.. null. --- V617F ---

3. The subject has a detectable JAK2 V617F mutation. --- V617F ---

Primary Outcomes

Measure: To determine the safety and maximum tolerated dose of a novel kinase inhibitor in subjects with myelofibrosis.

Time: 2 years

Measure: To estimate the efficacy of a novel kinase inhibitor in subjects with myelofibrosis, as determined by a reduction in JAK2 V617F allele frequency in peripheral blood neutrophils.

Time: 2 years

Secondary Outcomes

Measure: To estimate the incidence, severity, and attribution of treatment-emergent adverse events.

Time: 2 years

Measure: To estimate the rate of complete or major clinical-hematological response from treatment with Lestaurtinib (CEP-701) in this subject population as measured by the EUMNET response criteria.

Time: 2 years

7 A Phase II Study of MK-0683 in Patients With Polycythaemia Vera and Essential Thrombocythaemia.

The aim of the present study is to evaluate the efficacy and safety of MK-0683 in the treatment of PV and ET. This agent has most recently been shown to be a potent inhibitor of the autonomous proliferation of haematopoietic cells of PV and ET patients carrying the JAK2 V617F mutation. Accordingly, it may be anticipated that MK-0683 - by decreasing the JAK2 allele burden - may influence clonal myeloproliferation and in vivo granulocyte, platelet and endothelial activation , which are considered to be major determinants of morbidity and mortality ( thrombosis, bleeding, extramedullary haematopoiesis , myelofibrosis ) in these disorders. The effects of MK-0683 at the molecular level will be studied by global/ focused gene expression profiling, epigenome profiling and proteomics.

NCT00866762 Polycythemia Vera Essential Thrombocythemia Drug: HDAC inhibitor (MK-0683)
MeSH: Polycythemia Vera Polycythemia Thrombocytosis Thrombocythemia, Essential
HPO: Polycythemia Thrombocytosis

This agent has most recently been shown to be a potent inhibitor of the autonomous proliferation of haematopoietic cells of PV and ET patients carrying the JAK2 V617F mutation. --- V617F ---

Primary Outcomes

Measure: To evaluate the efficacy of study drug (MK-0683) in the treatment of patients with PV and ET.

Time: one year

Secondary Outcomes

Measure: To study changes in bone marrow morphology before and after treatment with study drug.

Time: one year

8 Molecular Study of Factors Involved in JAK-STAT Signalling Pathway in Familial Myeloproliferative Disorders

The main goal of the study is to progress in our understanding of the molecular basis of myeloproliferative disorders of the bone marrow (polycythemia vera, essential thrombocythemia, primary myelofibrosis). The study will focus on the genes encoding factors implicated in the JAK-STAT pathway which has an essential role in these diseases

NCT00873574 Myeloproliferative Disorders Biological: Blood samples and buccal swabs
MeSH: Myeloproliferative Disorders Disease
HPO: Myeloproliferative disorder

The recent identification of a recurrent activating tyrosine kinase mutation V617F in the JAK2 gene provides a breakthrough in the understanding of the molecular mechanisms of these diseases. --- V617F ---

The investigators have shown actually that the mutation V617F is a somatic one which is variably expressed among patients in the same family.Other somatic mutations and inherited factors, still unknown, may explain these discrepancies. --- V617F ---

JAK-STAT pathway has an essential role in non-CML MPD as was shown by the functional consequences of the V617F JAK2 mutation. --- V617F ---

Primary Outcomes

Measure: Allelic frequency comparison between the 2 cohorts

Time: At the inclusion visit

Secondary Outcomes

Measure: Undescribed gene mutations.

Time: At the inclusion visit

9 Phase II Trial of Oral Panobinostat (LBH589), a Novel Deacetylase Inhibitor (DACi) in Patients With Primary Myelofibrosis (PMF), Post Essential Thrombocythemia (ET) Myelofibrosis and Post- Polycythemia Vera (PV) Myelofibrosis

This study will assess the safety and efficacy of Panobinostat as a single agent in the treatment of Primary Myelofibrosis, Post-Polycythemia Vera and Post-Essential Thrombocythemia. There will be two cohorts - patients with JAK2 mutation and patients without JAK2 mutation.

NCT00931762 Primary Myelofibrosis Post-Polycythemia Vera Post-Essential Thrombocytopenia Drug: Panobinostat
MeSH: Polycythemia Vera Primary Myelofibrosis Thrombocytopenia Polycythemia
HPO: Polycythemia Thrombocytopenia

To compare the response to panobinostat in patients with the JAK2 V617F mutation to those without the JAK2 V617F mutation. --- V617F ---

To compare the response to panobinostat in patients with the JAK2 V617F mutation to those without the JAK2 V617F mutation. --- V617F --- --- V617F ---

(The presence of a JAK2 V617F mutation is not required for study entry) 2. Patients must meet the following laboratory criteria: - Patients can be either JAK2 V617F mutated or wild type - Serum potassium, magnesium, phosphorous, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution Note: Potassium, magnesium, phosphorous, sodium, and/or calcium supplements maybe given to correct values that are < LLN. --- V617F ---

(The presence of a JAK2 V617F mutation is not required for study entry) 2. Patients must meet the following laboratory criteria: - Patients can be either JAK2 V617F mutated or wild type - Serum potassium, magnesium, phosphorous, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution Note: Potassium, magnesium, phosphorous, sodium, and/or calcium supplements maybe given to correct values that are < LLN. --- V617F --- --- V617F ---

Primary Outcomes

Measure: To evaluate the overall response (CR, PR, and clinical improvement) to oral panobinostat as a single agent at 40 mg daily every Monday, Wednesday and Friday in patients with myelofibrosis.

Time: Upon enrollment of 13 participants into each cohort of the study and at the end of the study.

Secondary Outcomes

Measure: To compare the response to panobinostat in patients with the JAK2 V617F mutation to those without the JAK2 V617F mutation

Time: Upon enrollment of 13 participants into the study and at the end of the study

Measure: To evaluate the symptomatic improvement of myelofibrosis patients treated with panobinostat using the Myelofibrosis Symptom Assessment Form (MF-SAF) at baseline and after 2 and 4 months of treatment

Time: Upon enrollment of 13 participants in each cohort and at the end of the study

Measure: To evaluate the symptomatic improvement of myelofibrosis patients treated with panobinostat using the Myelofibrosis Symptom Assessment Form (MF-SAF) at baseline and after 2 and 4 months of treatment

Time: throughout the study

Measure: To assess compliance to panobinostat treatment as assessed by monthly capsule counts

Time: at the end of the study

10 A Phase I Study of Oral Arsenic Trioxide With or Without Ascorbic Acid in Adults With Myelofibrosis

This phase I trial studies the side effects and best dose of arsenic trioxide with or without ascorbic acid in treating patients with myelofibrosis. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving arsenic acid together with ascorbic acid may kill more cancer cells.

NCT01014546 Essential Thrombocythem Essential Thrombocythemia Polycythemia Vera Primary Myelofibrosis Drug: Arsenic Trioxide Dietary Supplement: Ascorbic Acid Other: Laboratory Biomarker Analysis Other: Pharmacological Study
MeSH: Polycythemia Vera Primary Myelofibrosis Polycythemia Thrombocytosis Thrombocythemia, Essential
HPO: Polycythemia Thrombocytosis

To estimate the efficacy of arsenic trioxide with ascorbic acid in subjects with myelofibrosis, as determined by a reduction in Janus kinase 2 (JAK2) V617F, JAK22T875N, and mutations of the thrombopoietin receptor (MPL515L/K) allele frequency in peripheral blood neutrophils. --- V617F ---

Primary Outcomes

Description: The frequency of toxicities will be tabulated by grade across all dose levels and courses. The frequency of toxicities will also be tabulated for the dose chosen as the MTD.

Measure: Adverse events, and their attribution throughout the study

Time: Up to 30 days post-treatment

Description: DLT is defined as any non-hematologic treatment-emergent grade 3 or greater adverse event deemed possibly, probably, or definitely related to the study drug. Exceptions are grade 3 nausea or vomiting, unless in the setting of maximal antiemetic treatment. Hematologic toxicities are not included in the definition of a DLT. The frequency of toxicities will be tabulated by grade across all dose levels and cycles.

Measure: Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 (Stage 1)

Time: At 28 days

Description: The frequency of toxicities will be tabulated by grade across all dose levels and cycles. The frequency of toxicities will also be tabulated for the dose chosen as the MTD.

Measure: Maximum tolerated dose (MTD), defined as the dose level at which 0 or 1 of 6 subjects experience DLT, and 2 of 3 or 2 of 6 experience DLT at the next higher dose level, assessed by the NCI CTC version 3.0 (Stage 1)

Time: At 28 days

Secondary Outcomes

Measure: Change in absolute number of circulating CD34+ cells in the peripheral blood (Stage 2 only)

Time: Baseline to 24 weeks

Measure: Change in JAK2/MPL (Stage 2 only)

Time: Baseline to 24 weeks

Description: Including: sVCAM-1, NE, MMP-2, MMP-9, SDF-1, TGF-B, and VEGF.

Measure: Change in plasma levels of chemokines as measured by ELISA (Stage 2)

Time: Baseline to 24 weeks

Description: Including: sVCAM-1, NE, MMP-2, MMP-9, SDF-1, TGF-B, and VEGF.

Measure: Change in plasma levels of cytokines as measured by ELISA (Stage 2)

Time: Baseline to 24 weeks

Description: Including: soluble vascular cell adhesion molecule 1 (sVCAM-1), neutrophil elastase (NE), matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), stromal cell derived growth factor-1 (SDF-1), TGF-B, and VEGF.

Measure: Change in plasma levels of proteases as measured by enzyme-linked immunosorbent assay (ELISA) (Stage 2)

Time: Baseline to 24 weeks

Measure: Disease response assessed using the IWG-MRT response criteria

Time: Up to 24 weeks

11 Phase II Trial of Erlotinib in Patients With JAK-2 V617F Positive Polycythemia Vera

The primary objective of this study is to determine the overall response rate to erlotinib in patients with polycythemia vera (PV). Response rate will be assessed by improvement in the complete blood count, ultrasound of the spleen, and JAK2 molecular status. It is purposed in this study to explore a possible molecular targeting of the driving mechanism of PV.

NCT01038856 Polycythemia Vera Drug: Erlotinib
MeSH: Polycythemia Vera Polycythemia
HPO: Polycythemia

Phase II Trial of Erlotinib in Patients With JAK-2 V617F Positive Polycythemia Vera. --- V617F ---

Trial of Erlotinib in Patients With JAK-2 V617F Positive Polycythemia Vera The primary objective of this study is to determine the overall response rate to erlotinib in patients with polycythemia vera (PV). --- V617F ---

Primary Outcomes

Measure: Overall Response Rate to Include Complete Hematological Response, Complete Molecular Response, Partial Hematological Response, and Minimal Hematological Response

Time: Day 15

Secondary Outcomes

Measure: Toxicity

Time: First assessment at day 15, subsequent assessments at 28 day intervals for an average of 1 year

Measure: Improvement in Splenomegaly Size

Time: 4 months, end of treatment and 12 months end of treatment

Measure: Decrease of Mutant JAK2V617F Allele Burden

Time: every 2 months until end of treatment and 12 months after end of treatment

12 A Phase 1 Study of LY2784544 in Patients With JAK2 V617F-Positive Myeloproliferative Disorders

The purpose of this study is to find out the safe dose range of the study drug in patients with myeloproliferative disorders.

NCT01134120 Myeloproliferative Disorders Thrombocythemia, Essential Polycythemia Vera Primary Myelofibrosis Drug: LY2784544
MeSH: Polycythemia Vera Primary Myelofibrosis Polycythemia Thrombocytosis Myeloproliferative Disorders Thrombocythemia, Essential
HPO: Myeloproliferative disorder Polycythemia Thrombocytosis

A Phase 1 Study of LY2784544 in Patients With JAK2 V617F-Positive Myeloproliferative Disorders. --- V617F ---

has post-ET MF - Have a quantifiable JAK2 V617F mutation - Have discontinued all previous approved therapies for myeloproliferative disorders, including any chemotherapy, immunomodulating therapy (for example, thalidomide, interferon-alpha), immunosuppressive therapy (for example, corticosteroids greater than 10 mg/day prednisone or equivalent), radiotherapy, and erythropoietin, thrombopoietin, or granulocyte colony stimulating factor for at least 14 days and recovered from the acute effects of therapy. --- V617F ---

Primary Outcomes

Measure: Determination of a recommended Phase 2 dosing regimen

Time: Time of first dose until last dose

Measure: Number of participants with clinical significant effects

Time: Time of first dose until last dose

Secondary Outcomes

Measure: Preliminary pharmacokinetics of LY2784544 (Cmax)

Time: Part A1: Day 1,2,15, and 29; Part A2: Day 7, 14, 21, 28, 29, 56, and 57; Part B: Day 1, 29, 57, and 113

Measure: Preliminary pharmacokinetics of LY2784544 (AUC)

Time: Part A1: Day 1,2,15, and 29; Part A2: Day 7, 14, 21, 28, 29, 56, and 57; Part B: Day 1, 29, 57, and 113

Measure: Malignant clone burden

Time: Part A1: Baseline (2 times), Weeks 13, 21 and every 6 months while patient is on study; Parts A2 and B: Baseline (2 times), Weeks 5, 8, 17, 25 and every 6 months while patient is on study

13 Single Arm Salvage Therapy With Pegylated Interferon Alfa-2a for Patients With High Risk Polycythemia Vera or High Risk Essential Thrombocythemia Who Are Either Hydroxyurea Resistant or Intolerant or Have Had Abdominal Vein Thrombosis

The aim of this research is to look at two conditions, Essential Thrombocythemia (ET) and Polycythemia Vera (PV). ET causes people to produce too many blood cells called platelets and PV causes too many platelets and red blood cells to be made. Platelets are particles which circulate in the blood stream and normally prevent bleeding and bruising. Having too many platelets in the blood increases the risk of developing blood clots, which can result in life threatening events like heart attacks and strokes. When the number of red blood cells is increased in PV this will slow the speed of blood flow in the body and increases the risk of developing blood clots. It is important for patients with ET or PV who are at risk of blood clots to receive drugs which will minimize the risks of developing these blood clots but at the moment the investigators are not sure which drugs will best control the disorder. The purpose of this study is to look at the effectiveness of giving patients who have been diagnosed with ET and PV a study drug regimen using Aspirin and PEGASYS (also known as Pegylated interferon alfa-2a, instead of the standard treatment drug called Hydroxyurea (or hydroxycarbamide or Hydroxyurea), for whom this drug may not be suitable. The drug may not be suitable either because it is not adequately controlling the number of blood cells or some specific side effects occur.

NCT01259817 High Risk Polycythemia Vera High Risk Essential Thrombocythemia Drug: PEGASYS Drug: Aspirin
MeSH: Polycythemia Vera Polycythemia Thrombocytosis Thrombocythemia, Essential
HPO: Polycythemia Thrombocytosis

To measure the impact of Pegylated Interferon Alfa-2a on JAK2-V617F, CALR, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities.. --- V617F ---

For these patients the following additional inclusion/exclusion criteria apply: - > 3 months since onset of SVT - SVT treated with oral anticoagulants but no aspirin - Liver enzymes not > 2 times the normal value - Absence of encephalopathy, refractory or infected ascites, esophageal varicose of grade > 1 at time of trial entry - Bone marrow biopsy confirmed diagnosis of PV or ET - JAK2-V617F mutations present - These patients may have a normal blood count at trial entry - Age over 18 years (no upper age limit) - Able and willing to comply with study criteria - Signed and informed consent to participant in this study - Willing to participate in associated correlative science biomarker study - Serum creatinine < 1.5 x upper limit of normal - AST and ALT < 2 x upper limit of normal - Total bilirubin within normal limits Exclusion Criteria: - Patients cannot have any other form of chemotherapy for their MPD (other than hydroxyurea). --- V617F ---

The point mutation in JAK2 encodes a valine to phenylalanine change at position 617 (JAK2 V617F), and confers constitutive tyrosine kinase activity. --- V617F ---

Introducing the mutation into the bone marrow of mouse models recapitulates the PV phenotype (complete with evolution to bone marrow fibrosis) and inhibitors of JAK2 attenuate the growth of cell lines bearing the mutation in vitro and in vivo, suggesting that JAK2 V617F is a pathophysiologically relevant therapeutic target. --- V617F ---

It is estimated that 95% of PV cases carry JAK2 V617F, while 50 to 60% of ET and PMF cases are JAK2 V617F+. --- V617F ---

Primary Outcomes

Measure: Evaluate the ability of Pegylated Interferon Alfa-2a to achieve Complete Response or Partial Response in patients with (1) high risk polycythemia vera or (2) high risk essential thrombocythemia or (3) splanchnic vein thrombosis

Time: 4 years

Secondary Outcomes

Measure: To evaluate the toxicity and tolerability of therapy Pegylated Interferon Alfa-2a in each of the 3 strata by recording the number of adverse events that occur during the study by using CTC 4.0 as the guide.

Time: 4 years

Measure: To measure the impact of Pegylated Interferon Alfa-2a on key biomarkers of the disease(s)by measuring the JAK2 allele burden.

Time: 4 years

Description: Improvement in disease symptoms will be measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) instrument being used in this study.

Measure: To evaluate specific pre-defined toxicity and tolerance of Pegylated Interferon Alfa-2a through a sequential structured symptom assessment package of patient reported outcome instruments.

Time: 4 years

Description: We plan to capture the rate of disease progression to a more advanced myeloid malignancy.

Measure: To estimate survival, and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation during therapy Pegylated Interferon Alfa-2a.

Time: 4 years

Description: Capture and record the cardiovascular events that occur during the study.

Measure: Estimate the observed incidence of major cardiovascular events during therapy Pegylated Interferon Alfa-2a.

Time: 4 years

Description: The impact of PEGASYS on JAK2 will be measured by the allele burden; hematopoietic cell clonality will be measured by whether patients with clonal disease return to polyclonal; bone marrow histopathology will be measured by going from abnormal to normal; cytogenetic abnormalities will be measured by seeing if the cytogenetics go from abnormal to normal.

Measure: To measure the impact of Pegylated Interferon Alfa-2a on JAK2-V617F, CALR, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities.

Time: 4 years

14 Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea Therapy in the Treatment of High Risk Polycythemia Vera (PV) and High Risk Essential Thrombocythemia (ET)

This research is looking at two conditions, Essential Thrombocythemia (ET) and Polycythemia Vera (PV). ET causes people to produce too many blood cells called platelets and PV causes too many platelets and red blood cells to be made. Platelets are particles which circulate in the blood stream and normally prevent bleeding and bruising. Having too many platelets in the blood increases the risk of developing blood clots, which can result in life threatening events like heart attacks and strokes. When the number of red blood cells is increased in PV this will slow the speed of blood flow in the body and increases the risk of developing blood clots. The purpose of this study is to look at the effectiveness of giving participants who have been diagnosed with ET or PV one of two different study regimens over time. The study subject will be followed for their condition for about 5 years. The subject will be randomized into one of two study regimens, either Pegylated Interferon Alfa-2a (PEGASYS) or Aspirin and Hydroxyurea (also called Hydroxycarbamide). The subject must be newly diagnosed or already receiving treatment for either PV or ET. Each of the study drugs used in this study is already being used to treat subjects with ET or PV currently, but the investigators are unsure which study drug is better.

NCT01259856 High Risk Polycythemia Vera High Risk Essential Thrombocythemia Drug: PEGASYS Drug: Hydroxyurea Drug: Aspirin
MeSH: Polycythemia Vera Polycythemia Thrombocytosis Thrombocythemia, Essential
HPO: Polycythemia Thrombocytosis

The impact of PEGASYS on JAK2 will be measured by the allele burden; hematopoietic cell clonality will be measured by whether patients with clonal disease return to polyclonal; bone marrow histopathology will be measured by going from abnormal to normal; cytogenetic abnormalities will be measured by seeing if the cytogenetics go from abnormal to normal.To compare the impact of therapy on JAK2-V617F (JAK2), CALR, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities.. Number of Participants With Progression of Disease or Death. --- V617F ---

Primary Outcomes

Description: Number of participants with Complete Remission after 12 months of therapy assessed by hematologic response rates two strata of patients with high risk polycythemia vera (PV) or high risk essential thrombocythemia (ET). Complete remission means no evidence of disease.

Measure: Number of Participants With Complete Remission (CR)

Time: 12 months

Description: Number of participants with Partial Remission after 12 months of therapy assessed by hematologic response rates two strata of patients with high risk polycythemia vera (PV) or high risk essential thrombocythemia (ET). Partial Remission means decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment.

Measure: Number of Participants With Partial Remission (PR)

Time: 12 months

Secondary Outcomes

Description: Number of Participants with Grade 3 and Grade 4 Hematological and Non-hematological Events using the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 to assess the toxicity, safety and tolerability of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea).

Measure: Number of Participants With Grade 3 and Grade 4 Hematological and Non-hematological Events

Time: 4 years

Description: Change in the Total Symptom Score which assessed improvement in disease symptoms measured by the change in TSS from the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) instrument being used in this study from baseline to 12 months. This 19 item instrument includes the previously validated 9 item brief fatigue inventory (BFI), symptoms related to splenomegaly, inactivity, cough, night sweats, pruritus, bone pains, fevers, weight loss, and an overall quality of life assessment. Each item is scored from 0-10 with full scale from 0-190, with higher scores mean worse symptoms.

Measure: Change in the Total Symptom Score (TSS)

Time: baseline and 12 months

Description: To compare the impact of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) on key biomarkers of the disease(s) by measuring the JAK2 allele burden.

Measure: JAK2 Allele Burden

Time: 4 years

Description: The impact of PEGASYS on JAK2 will be measured by the allele burden; hematopoietic cell clonality will be measured by whether patients with clonal disease return to polyclonal; bone marrow histopathology will be measured by going from abnormal to normal; cytogenetic abnormalities will be measured by seeing if the cytogenetics go from abnormal to normal.To compare the impact of therapy on JAK2-V617F (JAK2), CALR, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities.

Measure: Allele Burden

Time: 4 years

Description: Survival and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation after therapy To estimate survival and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation after therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) by capturing the rate of progression to a more advanced myeloid malignancy.

Measure: Number of Participants With Progression of Disease or Death

Time: 4 years

Measure: Number of Participants With Major Cardiovascular Events After Therapy

Time: 4 years

15 Natural Killer Cells and Polycythemia Vera (Vaquez's Disease)

Natural Killer cells (NK) are pivotal cells of innate immunity, that sense defective expression of HLA class I molecules and are complementary to specific cytotoxic T lymphocytes. A defect in NK cell cytotoxicity has been described in some hematopoietic malignancies such as acute myeloid leukemia, multiple myeloma, myelodysplastic syndroms. This defect is at least partially linked to a decreased or absent expression of some activating NK cell molecules, more particularly the so-called Natural Cytotoxicity Receptors (NCRs) NKp30, NKp44 and NKp46. Some old publications have demonstrated defective NK cytotoxicity in myeloproliferative syndroms (chronic myeloid leukemia, primary thrombocytosis, polycythemia vera). The investigators more particularly focused their attention on polycythemia vera (Vaquez's disease), a myeloproliferative disease characterized by the recently describet mutation V617F of the JAK2 tyrosine kinase. The investigators will precise the mechanisms leading to this cytotoxicity defect, the investigators also will evaluate the implication of V617F mutation on NK physiology, and will study the interactions between NK cells and hematopoietic progenitors.

NCT01284712 Polycythemia Vera Biological: blood sample
MeSH: Polycythemia Vera Polycythemia
HPO: Polycythemia

The investigators more particularly focused their attention on polycythemia vera (Vaquez's disease), a myeloproliferative disease characterized by the recently describet mutation V617F of the JAK2 tyrosine kinase. --- V617F ---

The investigators will precise the mechanisms leading to this cytotoxicity defect, the investigators also will evaluate the implication of V617F mutation on NK physiology, and will study the interactions between NK cells and hematopoietic progenitors. --- V617F ---

Primary Outcomes

Measure: To describe immunologic anomalies in polycythemia vera

Time: 2 years

16 An Exploratory, Observational, Multicentre Study to Investigate the Impact of the Presence of JAK2 (V617F) Mutation on Treatment Response in Patients With Essential Thrombocythaemia Treated With XAGRID® (Anagrelide Hydrochloride)

This study is hypothesis-generating to explore the impact of JAK2 (V617F) mutation status on the treatment response to anagrelide hydrochloride

NCT01352585 Essential Thrombocythemia (ET) Drug: Anagrelide hydrochloride
MeSH: Thrombocytosis Thrombocythemia, Essential
HPO: Thrombocytosis

An Exploratory, Observational, Multicentre Study to Investigate the Impact of the Presence of JAK2 (V617F) Mutation on Treatment Response in Patients With Essential Thrombocythaemia Treated With XAGRID® (Anagrelide Hydrochloride). --- V617F ---

Exploratory Multi-centre Trial In Patients With ET Treated With XAGRID® This study is hypothesis-generating to explore the impact of JAK2 (V617F) mutation status on the treatment response to anagrelide hydrochloride Number of Patients With Platelet Count ≤600x10^9/L After 12 Months. --- V617F ---

Primary Outcomes

Description: A platelet count of ≤600x10^9/L after 12 months is considered at least a partial response.

Measure: Number of Patients With Platelet Count ≤600x10^9/L After 12 Months

Time: 1 year

Secondary Outcomes

Description: A platelet count of ≤400x10^9/L after 12 months is considered a complete response.

Measure: Number of Patients With Platelet Count ≤400x10^9/L After 12 Months

Time: 1 year

Measure: Platelet Count

Time: 1 year

Measure: Red Blood Cell (RBC) Count

Time: 1 year

Measure: White Blood Cell (WBC) Count

Time: 1 year

Measure: Differential WBC Count

Time: 1 year

Measure: Hemoglobin Concentration

Time: 1 year

Measure: Hematocrit Level

Time: 1 year

17 Danish Study of Low-dose Interferon Alpha Versus Hydroxyurea in the Treatment of Philadelphia Chromosome Negative (Ph-)Chronic Myeloid Neoplasms.

The purpose of the study is to compare the efficacy and toxicity including quality of life of two types of low-dose interferon alpha compounds (PegIntron and Pegasys) with hydroxyurea (Hydrea), and to investigate the occurence of neutralizing antibodies against recombinant interferon.

NCT01387763 Polycythemia Vera Essential Thrombocythemia Primary Myelofibrosis Drug: PegIntron Drug: Pegasys Drug: PegIntron Drug: Pegasys Drug: Hydrea
MeSH: Polycythemia Vera Primary Myelofibrosis Polycythemia Thrombocytosis Thrombocythemia, Essential Neoplasms
HPO: Neoplasm Polycythemia Thrombocytosis

Molecular responses (JAK V617F allele burden) are assessed by qPCR according to the ELN guidelines.. toxicity (discontinuation of therapy due to intolerability). --- V617F ---

In 2005 major breakthrough in our understanding of the molecular pathophysiology was achieved with the identification of the JAK2 V617F mutation which is present in almost all patients with PV (98%) and about half of patients with ET and PMF. --- V617F ---

Within recent years IFN-alpha has demonstrated a capacity of inducing deep molecular remission (evaluated by JAK2 V617F qPCR) and normalisation of bone marrow morphology. --- V617F ---

If patients have a sustained deep molecular response (below 1 % JAK2 V617F mutated alleles for 12 months) therapy will be stopped to asses the sustainability of the remission off therapy.Patients over the age of 75 and intolerant or resistant to hydroxyurea will be offered rescue treatment with orally busulfan (Myleran). --- V617F ---

Primary Outcomes

Description: Molecular responses (JAK V617F allele burden) are assessed by qPCR according to the ELN guidelines.

Measure: molecular response (changes from baseline)

Time: 18, 36 and 60 months

Secondary Outcomes

Description: The proportion of patients treated with PegIntron, Pegasys and Hydrea who need to discontinue therapy due to intolerability

Measure: toxicity (discontinuation of therapy due to intolerability)

Time: 18 months

Description: Quality of life will be evaluated according to EORTC QLQ C-30 and MPN-SAF

Measure: Quality of life (changes from baseline)

Time: 4, 12, 24, 36, 48 and 60 months

Description: A bone marrow sample will be evaluated in order to detect and grade changes in bone marrow morphology.

Measure: Histopathological response (changes from baseline)

Time: 36 and 60 months

Description: investigation of the sustainability of an obtained molecular remission (< 1% JAK2V617F mutated alleles) after discontinuation of interferon- alpha( Pegasys, PegIntron, Multiferon) or Hydrea.

Measure: Sustained molecular response (changes from level at time of discontinuation of therapy)

Time: 12, 24 and 36 months

Description: Proportion of patients treated with Peintron and Pegasys who have developed neutralizing antibodies.

Measure: Neutralizing antibodies against PegIntron and Pegasys

Time: 24 months

Description: Hematological response will be evaluated according to the ELN guidelines.

Measure: hematological response

Time: 12 months

18 A Phase II, Multicenter, Open Label, Single Arm Study of SAR302503 in Subjects Previously Treated With Ruxolitinib and With a Current Diagnosis of Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Primary Objective: - To evaluate the efficacy of once daily dose of SAR302503 in subjects previously treated with ruxolitinib and with a current diagnosis of intermediate-1 with symptoms, Intermediate-2 or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF), or post-essential thrombocythemia myelofibrosis (Post-ET MF) based on the reduction of spleen volume at the end of 6 treatment cycles; Secondary Objectives: - To evaluate the effect of SAR302503 on Myelofibrosis (MF) associated symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary - To evaluate the durability of splenic response - To evaluate the splenic response to SAR302503 by palpation at the end of Cycle 6 - To evaluate the splenic response to SAR302503 at the end of Cycle 3 - To evaluate the effect of SAR302503 on the Janus kinase 2 (JAK2) V617F allele burden - To evaluate the safety and tolerability of SAR302503 in this population - To evaluate plasma concentrations of SAR302503 for population PK analysis, if warranted

NCT01523171 Hematopoietic Neoplasm Drug: SAR302503
MeSH: Hematologic Neoplasms Primary Myelofibrosis
HPO: Hematological neoplasm Leukemia

Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib Primary Objective: - To evaluate the efficacy of once daily dose of SAR302503 in subjects previously treated with ruxolitinib and with a current diagnosis of intermediate-1 with symptoms, Intermediate-2 or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF), or post-essential thrombocythemia myelofibrosis (Post-ET MF) based on the reduction of spleen volume at the end of 6 treatment cycles; Secondary Objectives: - To evaluate the effect of SAR302503 on Myelofibrosis (MF) associated symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary - To evaluate the durability of splenic response - To evaluate the splenic response to SAR302503 by palpation at the end of Cycle 6 - To evaluate the splenic response to SAR302503 at the end of Cycle 3 - To evaluate the effect of SAR302503 on the Janus kinase 2 (JAK2) V617F allele burden - To evaluate the safety and tolerability of SAR302503 in this population - To evaluate plasma concentrations of SAR302503 for population PK analysis, if warranted Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at the end of Cycle 6 as measured by Magnetic Resonance Imaging (MRI) (or CT scan in subjects with contraindications for MRI). --- V617F ---

Primary Outcomes

Measure: Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at the end of Cycle 6 as measured by Magnetic Resonance Imaging (MRI) (or CT scan in subjects with contraindications for MRI)

Time: 6 months

Secondary Outcomes

Measure: Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction from baseline to the end of Cycle 6 in the total symptom score using the modified MFSAF

Time: 6 months

Measure: Duration of spleen response, measured by MRI (or CT scan in subjects with contraindications for MRI)

Time: 6 months

Measure: Proportion of subjects with a ≥50% reduction in length of spleen by palpation from baseline at the end of Cycle 6

Time: 6 months

Measure: Response Rate at the end of Cycle 3, defined as the proportion of subjects who have a ≥35% reduction from baseline in volume of spleen at the end of Cycle 3 as measured by MRI (or CT scan in subjects with contraindications for MRI)

Time: 6 months

Measure: Percent change of spleen volume at the end of Cycles 3 and 6 from baseline as measured by MRI (or CT scan in subjects with contraindications for MRI)

Time: 6 months

Measure: Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03

Time: approximately 5 years

Measure: Plasma concentrations of SAR302503

Time: 4 months

Measure: The effect of SAR302503 on the JAK2V617F allele burden

Time: 2 years

19 A Phase 2 Study of LY2784544 in Patients With Myeloproliferative Neoplasms

The primary purpose of this study is to measure the response rate in participants with the myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF) when treated with LY2784544, including those who have demonstrated an intolerance to, failure of primary response to, or have demonstrated disease progression while on ruxolitinib.

NCT01594723 Neoplasms, Hematologic Drug: 120 mg LY2784544
MeSH: Hematologic Neoplasms Myeloproliferative Disorders Neoplasms
HPO: Hematological neoplasm Leukemia Myeloproliferative disorder Neoplasm

Inclusion Criteria: - Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF) as defined by the World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Swerdlow et al. 2008) and meet the following additional subtype specific criteria: - PV: have failed or is intolerant of standard therapies or refuses to take standard medications - ET: have failed or is intolerant of standard therapies or refuses to take standard medications - MF (participants with MF must meet at least 1 of the following): have intermediate 1, intermediate 2, or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPPS Plus) for Primary Myelofibrosis (Gangat et al. 2011); or have symptomatic MF with spleen greater than 10 centimeter (cm) below left costal margin; or have post-polycythemic MF; or have post-ET MF - All PV, ET, and MF participants must meet the following criteria: o Have a quantifiable level of janus kinase 2 with a valine to phenylalanine substitution at amino acid 617 (JAK2 V617F) mutation. --- V617F ---

This inclusion criterion will not apply to the subset of participants in Cohorts 10 and 11 that must be negative for the JAK2 V617F mutation - Are ≥ 18 years of age - Have given written informed consent prior to any study-specific procedures - Have adequate organ function, including: Hepatic: Direct bilirubin ≤1.5 times upper limits of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) ≤2.5 times ULN; Renal: Serum creatinine ≤1.5 times ULN; Bone Marrow Reserve: Absolute neutrophil count (ANC) ≥1000/microliter (mcL), platelets ≥50,000/mcL for participants with ET or PV and ≥25,000/mcL for participants with MF - Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale - Have discontinued all previous approved therapies for Myeloproliferative Neoplasms (MPNs), including any chemotherapy, immunomodulating therapy (for example, thalidomide, interferon-alpha), immunosuppressive therapy (for example, corticosteroids >10 mg/day prednisone or equivalent), radiotherapy, and erythropoietin, thrombopoietin, or granulocyte colony stimulating factor for at least 14 days and recovered from the acute effects of therapy. --- V617F ---

An exception to this criterion will be allowed for participants with a prior history of Budd-Chiari Syndrome who are being treated with warfarin or one of its derivatives - Have received a hematopoietic stem cell transplant - Have a second primary malignancy that in the judgment of the Investigator and Sponsor may affect the interpretation of results - Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required) - Have a history of congestive heart failure with New York Heart Association (NYHA) Class >2 (NYHA Class 1 and 2 are eligible), unstable angina, recent myocardial infarction (within 6 months prior to administration of study drug), or documented history of ventricular arrhythmia Inclusion Criteria: - Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF) as defined by the World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Swerdlow et al. 2008) and meet the following additional subtype specific criteria: - PV: have failed or is intolerant of standard therapies or refuses to take standard medications - ET: have failed or is intolerant of standard therapies or refuses to take standard medications - MF (participants with MF must meet at least 1 of the following): have intermediate 1, intermediate 2, or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPPS Plus) for Primary Myelofibrosis (Gangat et al. 2011); or have symptomatic MF with spleen greater than 10 centimeter (cm) below left costal margin; or have post-polycythemic MF; or have post-ET MF - All PV, ET, and MF participants must meet the following criteria: o Have a quantifiable level of janus kinase 2 with a valine to phenylalanine substitution at amino acid 617 (JAK2 V617F) mutation. --- V617F ---

Primary Outcomes

Measure: Percentage of Participants with an Objective Response (Objective Response Rate)

Time: Baseline until Disease Progression (PD) or Participant Stops Study (Estimated up to 24 Months)

Secondary Outcomes

Measure: Percentage of Participants with a Molecular Response (Molecular Response Rate)

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Percentage of Participants with Hematological Improvement (Hematological Improvement Rate)

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Change in Spleen Size

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Change in Bone Marrow Fibrosis Grade

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Change in Number of Thrombotic or Hemorrhagic Events

Time: 3 Months prior to Study Drug (historic) until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Change in Number of Phlebotomies and Transfusions

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Duration of Response

Time: Confirmed Response to PD or Death from Any Cause (Estimated up to 24 Months)

Measure: Time to Best Response

Time: Baseline to Confirmed Response (Estimated up to 6 Months)

Measure: Change in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Time to Treatment Failure

Time: Baseline to PD, Death from Any Cause or Participant Stops Study (Estimated up to 24 Months)

Measure: Time to Disease Progression

Time: Baseline to Measured PD (Estimated up to 24 Months)

Measure: Progression Free Survival (PFS)

Time: Baseline to PD or Death from Any Cause (Estimated up to 24 Months)

Measure: Change in Activities of Daily Living (ADL)/ Instrumental Activities of Daily Living (IADL)

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Change in EuroQol - 5 dimensions (EQ-5D) Index Score

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Change in International Prognosis Scoring System Scales (IPSS)

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2784544

Time: Predose up to Day 84

Measure: PK: Time of Maximal Concentration (Tmax) of LY2784544

Time: Predose up to Day 84

Measure: Change in Liver Size

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

Measure: Change in 6-item Physician Symptom Assessment

Time: Baseline until PD or Participant Stops Study (Estimated up to 24 Months)

20 A Large-scale Trial Testing the Intensity of CYTOreductive Therapy to Prevent Cardiovascular Events In Patients With Polycythemia Vera (PV)

CYTO-PV is a phase III Prospective, Randomized, Open-label, with Blinded Endpoint evaluation (PROBE), multi-center, clinical trial in patients with diagnosis of Polycythemia vera (PV) treated at the best of recommended therapies (e.g.adequate control of standard cardiovascular risk factors). Irrespective of randomized interventions, all patients will be administered low-dose aspirin (when not contraindicated), i.e.the standard antithrombotic treatment in PV patients. The purpose of this study to demonstrate that a more intensive cytoreductive therapy, plus low-dose aspirin when not contraindicated, with phlebotomy and/or hydroxyurea (HU), aimed at maintaining hematocrit (HCT) < 45% is more effective than a less intensive cytoreduction (either with phlebotomy or HU plus low-dose aspirin when not contraindicated) maintaining HCT in the range of 45-50% in the reduction of CV deaths plus thrombotic events (stroke, acute coronary syndrome [ACS], transient ischemic attack [TIA], pulmonary embolism [PE], splanchnic thrombosis, deep vein thrombosis [DVT], and any other clinically relevant thrombotic event), in patients with Polycythemia Vera treated at the best of recommended therapies (e.g. adequate control of standard cardiovascular risk factors).

NCT01645124 Polycythemia Vera Drug: Hydroxyurea Procedure: Phlebotomy
MeSH: Polycythemia Vera Polycythemia
HPO: Polycythemia

However, both pragmatic reasons and the consideration of the clinical condition under study (see: age, comorbidity, polytherapy) support the decision to adopt a generalized policy of surveillance specifically on: Hypotension or syncope after phlebotomy; renal dysfunction (creatinine); liver dysfunction (ALT, AST, symptoms); White blood cell count; Platelet count; Bleeding.. Inclusion Criteria: Males and females aged 18 years or more are eligible for the study if they meet all the following inclusion criteria: - New diagnosis of PV according to WHO 2007 diagnostic criteria including Jak 2 V617F mutation status; - Old diagnosis of PV confirmed with JAK-2 positivity and clinical course of the disease; - Ability and willingness to comply with all study requirements; - Written informed consent (obtained before any study specific procedure). --- V617F ---

Inclusion Criteria: Males and females aged 18 years or more are eligible for the study if they meet all the following inclusion criteria: - New diagnosis of PV according to WHO 2007 diagnostic criteria including Jak 2 V617F mutation status; - Old diagnosis of PV confirmed with JAK-2 positivity and clinical course of the disease; - Ability and willingness to comply with all study requirements; - Written informed consent (obtained before any study specific procedure). --- V617F ---

Primary Outcomes

Description: To demonstrate that in patients with PV treatment with aggressive cytoreductive therapy aimed at maintaining HCT < 45% is more effective than cytoreductive therapy aimed at maintaining HCT between 45 and 50% in the reduction CV deaths plus thrombotic events (PEP: stroke, acute coronary syndrome [ACS], transient ischemic attack [TIA], pulmonary embolism [PE], abdominal thrombosis, deep vein thrombosis [DVT], and peripheral arterial thrombosis). The minimum clinically relevant beneficial effect is set at a 30% reduction of risk of the PEP.

Measure: Reduction of PEP (Primary End Point)defined as CV deaths plus thrombotic events

Time: Expected average of 5 years

Secondary Outcomes

Description: The events included in the PEP, arterial and venous thrombosis, major and minor thrombosis as well as hospitalization for any reason, hospitalization for CV reason, malignancy and PV-related malignancy (progression to myelofibrosis, myelodysplastic or leukemic transformation) will be analyzed separately to assess the full benefit/risk profile of experimental treatments.

Measure: PEP plus minor thrombosis, hospitalization and malignancy

Time: Expected average of 5 years

Other Outcomes

Description: Background knowledge suggests that no specific safety precautions are to be adopted for phlebotomy and HU administration. However, both pragmatic reasons and the consideration of the clinical condition under study (see: age, comorbidity, polytherapy) support the decision to adopt a generalized policy of surveillance specifically on: Hypotension or syncope after phlebotomy; renal dysfunction (creatinine); liver dysfunction (ALT, AST, symptoms); White blood cell count; Platelet count; Bleeding.

Measure: Aadverse Events

Time: Expected average of 5 years

21 Long-term Study Evaluating the Effect of Givinostat in Patients With JAK2V617F Positive Chronic Myeloproliferative Neoplasms

This is a multicenter, open label, long-term study testing the long-term safety, tolerability and efficacy of Givinostat in patients with Polycythemia Vera, Essential Thrombocythemia, primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis following core protocols in chronic myeloproliferative neoplasms and/or patient-named compassionate use program (if regulated/allowed by the local regulations, e.g. for Italy D.M. 8/5/2003 "Uso terapeutico di medicinale sottoposto a sperimentazione clinica" published on G.U. n. 173 of 28 July 2003, and the following amendments). Patients will continue at their last tolerable dose and treatment schedule of Givinostat monotherapy. If patients previously received Givinostat in combination with other drugs during a core protocol or a compassionate use program (if regulated/allowed by the local regulations, e.g. for Italy D.M. 8/5/2003 "Uso terapeutico di medicinale sottoposto a sperimentazione clinica" published on G.U. n. 173 of 28 July 2003, and the following amendments), they will be treated at the last tolerable dose of the combination. Assessment of safety and efficacy will be performed at each quarterly visit and each visit will also include laboratory tests and ECG examination. During the visits the clinical benefit will be assessed by Investigator according to the revised European LeukemiaNet response criteria (for PV and ET) and EUMNET response criteria (for MF). The dose of Givinostat will be modified for protocol specified toxicities. The treatment may continue up to Marketing Authorization of Givinostat, currently planned in the next 5 years (note: only for Germany, this long-term study is initially limited up to 2 years of treatment). Patients may discontinue study treatment at any time and remain on study therapy as long as they derive clinical benefit. Safety will be monitored at each visit throughout the entire duration of the study. In case the approved label will not cover the whole study population, Givinostat will be provided by the Sponsor to those patients not fulfilling the criteria for the approved label of the drug that are still deriving benefit from Givinostat at the time of its commercial availability.

NCT01761968 Chronic Myeloproliferative Neoplasms Drug: Givinostat
MeSH: Myeloproliferative Disorders Neoplasms
HPO: Myeloproliferative disorder Neoplasm

reduction of the allele burden of the mutated Janus Kinase 2 in the position V617F). --- V617F ---

Primary Outcomes

Description: To obtain information on the long-term efficacy of Givinostat in patients with chronic myeloproliferative neoplasms following core protocols or compassionate use program: Number of patients experiencing adverse events; Type, incidence, and severity of treatment-related adverse events. To determine the long term safety and tolerability of Givinostat in patients with chronic myeloproliferative neoplasms following core protocols or compassionate use program: For Polycythemia Vera and Essential Thrombocythemia, Complete response and partial response rate according to the revised clinico-haematological European LeukemiaNet response criteria; For Myelofibrosis, complete response, major response, moderate response and minor response rate according to European Myelofibrosis Network response criteria. Note that these assessment will be repeated periodically (each 3 months) during the study. In fact, the treatment will continue up to Marketing Authorisation of Givinostat.

Measure: Long-term safety and efficacy

Time: 3 months

Other Outcomes

Description: To evaluate the effect of Givinostat on each single response parameter according to the revised European LeukemiaNet (for Polycythemia Vera and Essential Thrombocythemia) and European European Myelofibrosis Network response criteria (for Myelofibrosis). Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of Givinostat.

Measure: Clinical exploratory endpoint

Time: 1 year

Description: To evaluate the molecular response (i.e. reduction of the allele burden of the mutated Janus Kinase 2 in the position V617F). Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of Givinostat.

Measure: Molecular exploratory endpoint

Time: 1 year

Description: To identify potential other markers predictive of clinical benefit of Givinostat (e.g. potential pharmacodynamic markers). Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of Givinostat.

Measure: Biomolecular exploratory endpoint

Time: 1 year

22 A Two-part Study Top Assess the Safety and Preliminary Efficacy of Givinostat in Patients With JAK2V617F Positive Polycythemia Vera

This is a two-part, multicenter, open label, non-randomized, phase Ib/II study to assess the safety and tolerability, Maximum Tolerated Dose and preliminary efficacy of Givinostat in patients with JAK2V617F positive Polycythemia Vera. Part A is the dose finding part while Part B is assessing the preliminary efficacy. Patients will be enrolled either in Part A or Part B and transition from one part to the other is not allowed. Eligible patients for this study will have a confirmed diagnosis of Polycythemia Vera according to the revised World Health Organization criteria. Only if the enrolment in Part A is slow (i.e. < 5 patients enrolled in 3 months), eligibility for this part of the study may be expanded to all patients with chronic myeloproliferative neoplasms. Study therapy will be administered in 28 day cycles (4 weeks of treatment). Disease response will be evaluated according to the European LeukemiaNet criteria after 3 and 6 cycles (i.e. at weeks 12 and 24, respectively) of treatment with Givinostat for both parts of the study. All phlebotomies performed in the first 3 weeks of treatment will not be counted to assess the clinico-haematological response. The study will last up to a maximum of 24 weeks of treatment. However, after completion of the trial, all patients achieving clinical benefit will be allowed to continue treatment with Givinostat (at the same dose and schedule) in a long-term study. Safety will be monitored at each visit throughout the entire duration of the study. Treatment will be administered on an outpatient basis and patients will be followed regularly with physical and laboratory tests, as specified in the protocol; in case of hospitalization, the treatment will be continued or interrupted according to the Investigators' decision.

NCT01901432 Polycythemia Vera Drug: Givinostat
MeSH: Polycythemia Vera Polycythemia
HPO: Polycythemia

dose group was not available for PK analysis.. Inclusion Criteria: 1. Patients must be able to provide informed consent and be willing to sign an informed consent form; 2. Patients must have an age ≥18 years; 3. Patients must have a confirmed diagnosis of Polycythemia Vera according to the revised World Health Organization criteria; 4. Patients must have mutated Janus Kinase 2 (mutation V617F) positive disease; 5. Patients must have an active/not controlled disease defined as 1. hematocrit ≥ 45% or hematocrit <45% in need of phlebotomy, and 2. platelet count > 400 x109/L, and 3. white blood cell count > 10 x109/L; 6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 in Part A, ECOG performance status ≤ 2 in Part B within 7 days of initiating study drug; 7. Female patient of childbearing potential has a negative serum or urine pregnancy test within 72 hours of the first dose of study therapy; 8. Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential; 9. Adequate and acceptable organ function within 7 days of initiating study drug; 10. --- V617F ---

Inclusion Criteria: 1. Patients must be able to provide informed consent and be willing to sign an informed consent form; 2. Patients must have an age ≥18 years; 3. Patients must have a confirmed diagnosis of Polycythemia Vera according to the revised World Health Organization criteria; 4. Patients must have mutated Janus Kinase 2 (mutation V617F) positive disease; 5. Patients must have an active/not controlled disease defined as 1. hematocrit ≥ 45% or hematocrit <45% in need of phlebotomy, and 2. platelet count > 400 x109/L, and 3. white blood cell count > 10 x109/L; 6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 in Part A, ECOG performance status ≤ 2 in Part B within 7 days of initiating study drug; 7. Female patient of childbearing potential has a negative serum or urine pregnancy test within 72 hours of the first dose of study therapy; 8. Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential; 9. Adequate and acceptable organ function within 7 days of initiating study drug; 10. --- V617F ---

Primary Outcomes

Description: Evaluations were performed on the type, incidence and severity of TEAEs, graded according to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03, following administration of givinostat for up to 6 cycles of treatment in Part A. Grades 1 through 5 were as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening or requiring hospitalisation; Grade 4: Life threatening consequences; Grade 5: Death related to AE. Results are reported as number of patients with TEAEs for each of the indicated categories. Definitions: drug-related TEAE / treatment-emergent serious adverse event (TESAE) corresponded to reasonable suspicion that the TEAE / TESAE was associated with the use of the study drug, according to investigator assessment; discontinuation refers to discontinuation from treatment.

Measure: Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) in Part A of the Study

Time: 168 days (up to Cycle 6 Day 28 in Part A).

Description: The MTD of givinostat was based only on Cycle 1 DLTs. A DLT was defined as the following drug-related toxicity: Grade 4 hematological toxicity, or Grade 3 febrile neutropenia, or Grade ≥3 non-hematological toxicity (with the exception Grade 3 diarrhea without adequate supportive care lasting less than 3 days, and Grade 3 nausea or vomiting without adequate supportive care lasting less than 3 days), or Any drug-related serious AE, or Any toxicity clearly not related to disease progression or intercurrent illness requiring interruption of dosing for more than 3 days during first cycle. At end of Cycle 1, for the third patient in each DL, the safety of the 3 patients treated for 1 cycle was reviewed and it was decided if the dose should be escalated or not. Results are reported as the number of patients with DLT events for Cycle 1 in Part A.

Measure: Number of Dose Limiting Toxicities (DLTs) After 1 Cycle in Part A of the Study

Time: 28 days (up to Cycle 1 Day 28 in Part A).

Description: Evaluations were performed on the type, incidence and severity of TEAEs, graded according to CTCAE v. 4.03, following administration of givinostat at the MTD for up to 3 cycles of treatment in Part B. Grades 1 through 5 were as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening or requiring hospitalisation; Grade 4: Life threatening consequences; Grade 5: Death related to AE. Results are reported as number of patients with TEAEs for each of the indicated categories. Definitions: drug-related TEAE / TESAE corresponded to reasonable suspicion that the TEAE / TESAE was associated with the use of the study drug, according to investigator assessment; discontinuation refers to discontinuation from treatment.

Measure: Number of Patients Experiencing TEAEs After 3 Cycles in Part B of the Study

Time: 84 days (up to Cycle 3 Day 28 in Part B).

Description: ORR, CR and PR following administration of givinostat at MTD for 3 cycles in Part B, reported as percentage of patients with a response. Response was evaluated according to the clinico-hematological European LeukemiaNet (ELN) response criteria. If Investigator's clinical response assessment (taking into account the overall medical judgment of the specific patient's case) was not in agreement with exact application of the ELN response criteria, the Investigator's assessment superseded the mathematical application of these criteria and was used for analysis. CR defined as: Hematocrit (HCT) <45% without phlebotomy, and Platelets ≤400 x10^9/litre (L), and White Blood Cell count ≤10 x10^9/L, and Normal spleen size, and No disease-related systemic symptoms (i.e. pruritus, headache, microvascular disturbances). PR defined as: Patients not fulfilling CR and HCT <45% without phlebotomy, or Response in ≥3 other criteria.

Measure: Overall Response Rate (ORR) (i.e. Complete Response [CR] and Partial Response [PR]) After 3 Cycles in Part B of the Study

Time: 84 days (up to cycle 3 Day 28 in Part B).

Secondary Outcomes

Description: ORR following administration of givinostat after 3 cycles and after 6 cycles in Part A, reported as percentage of patients with a response. Response was evaluated according to the clinico-hematological ELN response criteria. If Investigator's clinical response assessment (taking into account the overall medical judgment of the specific patient's case) was not in agreement with exact application of the ELN response criteria, the Investigator's assessment superseded the mathematical application of these criteria and was used for analysis. Analysis performed using the dataset for all Part A patients combined.

Measure: ORR After 3 Cycles and After 6 Cycles in Part A of the Study

Time: 84 and 168 days (up to Cycle 3 Day 28 and Cycle 6 Day 28 in Part A).

Description: ORR following administration of givinostat at the MTD for 6 cycles in Part B, reported as percentage of patients with a response. Response was evaluated according to the clinico-hematological ELN response criteria. If Investigator's clinical response assessment (taking into account the overall medical judgment of the specific patient's case) was not in agreement with exact application of the ELN response criteria, the Investigator's assessment superseded the mathematical application of these criteria and was used for analysis.

Measure: ORR After 6 Cycles in Part B of the Study

Time: 168 days (up to Cycle 6 Day 28 in Part B).

Description: Evaluations were performed on the type, incidence and severity of TEAEs, graded according to CTCAE v. 4.03, following administration of givinostat at the MTD for up to 6 cycles of treatment in Part B. Grades 1 through 5 were as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening or requiring hospitalisation; Grade 4: Life threatening consequences; Grade 5: Death related to AE. Results are reported as number of patients with TEAEs for each of the indicated categories. Definitions: drug-related TEAE / TESAE corresponded to reasonable suspicion that the TEAE / TESAE was associated with the use of the study drug, according to investigator assessment; discontinuation refers to discontinuation from treatment. Results are reported as number of patients with TEAEs for each of the indicated categories.

Measure: Number of Patients Experiencing TEAEs After 6 Cycles in Part B of the Study

Time: 168 days (up to Cycle 6 Day 28 in Part B).

Description: Pharmacokinetic (PK) evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of Cmax following administration of givinostat for 1 cycle in Part A. PK calculations were performed by standard non-compartmental analysis. Results are reported for Cycle 1 Day 1 and Cycle 1 Day 28. Note: concentration data for ITF2374 (Cycle 1 Day 1 and Cycle 1 Day 28) and for ITF2375 (Cycle 1 Day 1) in the DL0 dose group of Part A were not available for PK analysis.

Measure: Assessment of Maximum Plasma Concentration (Cmax) of Givinostat and Metabolites (ITF2374 and ITF2375) in Part A of the Study

Time: Blood samples were collected in Part A on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 1 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of Tmax following administration of givinostat for 1 cycle in Part A. PK calculations were performed by standard non-compartmental analysis. Results are reported for Cycle 1 Day 1 and Cycle 1 Day 28. Note: concentration data for ITF2374 (Cycle 1 Day 1 and Cycle 1 Day 28) and for ITF2375 (Cycle 1 Day 1) in the DL0 dose group of Part A were not available for PK analysis.

Measure: Assessment of Time to Maximum Plasma Concentration (Tmax) of Givinostat and Metabolites (ITF2374 and ITF2375) in Part A of the Study

Time: Blood samples were collected in Part A on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 1 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of Tlast following administration of givinostat for 1 cycle in Part A. PK calculations were performed by standard non-compartmental analysis. Results are reported for Cycle 1 Day 1 and Cycle 1 Day 28. Note: concentration data for ITF2374 (Cycle 1 Day 1 and Cycle 1 Day 28) and for ITF2375 (Cycle 1 Day 1) in the DL0 dose group of Part A were not available for PK analysis.

Measure: Assessment of Time of the Last Detectable Concentration (Tlast) of Givinostat and Metabolites (ITF2374 and ITF2375) in Part A of the Study

Time: Blood samples were collected in Part A on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 1 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of AUClast following administration of givinostat for 1 cycle in Part A. PK calculations were performed by standard non-compartmental analysis and AUClast was calculated using the linear trapezoidal rule. Results are reported for Cycle 1 Day 1 and Cycle 1 Day 28. Note: concentration data for ITF2374 (Cycle 1 Day 1 and Cycle 1 Day 28) and for ITF2375 (Cycle 1 Day 1) in the DL0 dose group of Part A were not available for PK analysis.

Measure: Assessment of Area Under Plasma Concentration Versus the Time Curve up to the Last Detectable Concentration (AUClast) of Givinostat and Metabolites (ITF2374 and ITF2375) in Part A of the Study

Time: Blood samples were collected in Part A on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 1 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of AUC0-12 following administration of givinostat for 1 cycle in Part A. PK calculations were performed by standard non-compartmental analysis and AUC0-12 was calculated using the linear trapezoidal rule. Results are reported for Cycle 1 Day 1 and Cycle 1 Day 28. Note:concentration data for ITF2374 (Cycle 1 Day 1 and Cycle 1 Day 28) across all dose groups and for ITF2375 (Cycle 1 Day 1) in the DL0 dose group of Part A were not available for PK analysis.

Measure: Assessment of Area Under Plasma Concentration Versus the Time Curve in the Dosing Interval (0-12 Hours) (AUC0-12) of Givinostat and Metabolites (ITF2374 and ITF2375) in Part A of the Study

Time: Blood samples were collected in Part A on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 1 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of Cmax following administration of givinostat for 2 cycles in Part B. PK calculations were performed by standard non-compartmental analysis. Following definition of the MTD in Part A, during Part B Cycle 1, givinostat was administered at 100 mg b.i.d. and during Part B Cycle 2 was administered at 100 mg, 75 mg and 50 mg b.i.d. (since dose reductions due to TEAEs were allowed from Cycle 2 onwards, as per protocol). Results are reported for Cycle 1 Day 1 and Cycle 2 Day 28 for the doses administered during Part B. Note: PK evaluation for the givinostat 75 mg and 50 mg b.i.d. dose groups for Cycle 1 Day 1 was not applicable (since all received givinostat 100 mg b.i.d.). Additionally, concentration data for ITF2375 (Cycle 1 Day 28) in the 50 mg b.i.d. dose group was not available for PK analysis.

Measure: Assessment of Cmax of Givinostat and Metabolites (ITF2374 and ITF2375) in Part B of the Study

Time: Blood samples were collected in Part B on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 2 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of Tmax following administration of givinostat for 2 cycles in Part B. PK calculations were performed by standard non-compartmental analysis. Following definition of the MTD in Part A, during Part B Cycle 1, givinostat was administered at 100 mg b.i.d. and during Part B Cycle 2 was administered at 100 mg, 75 mg and 50 mg b.i.d. (since dose reductions due to TEAEs were allowed from Cycle 2 onwards, as per protocol). Results are reported for Cycle 1 Day 1 and Cycle 2 Day 28 for the doses administered during Part B. Note: PK evaluation for the givinostat 75 mg and 50 mg b.i.d. dose groups for Cycle 1 Day 1 was not applicable (since all received givinostat 100 mg b.i.d.). Additionally, concentration data for ITF2375 (Cycle 1 Day 28) in the 50 mg b.i.d. dose group was not available for PK analysis.

Measure: Assessment of Tmax of Givinostat and Metabolites (ITF2374 and ITF2375) in Part B of the Study

Time: Blood samples were collected in Part B on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 2 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of Tlast following administration of givinostat for 2 cycles in Part B. PK calculations were performed by standard non-compartmental analysis. Following definition of the MTD in Part A, during Part B Cycle 1, givinostat was administered at 100 mg b.i.d. and during Part B Cycle 2 was administered at 100 mg, 75 mg and 50 mg b.i.d. (since dose reductions due to TEAEs were allowed from Cycle 2 onwards, as per protocol). Results are reported for Cycle 1 Day 1 and Cycle 2 Day 28 for the doses administered during Part B. Note: PK evaluation for the givinostat 75 mg and 50 mg b.i.d. dose groups for Cycle 1 Day 1 was not applicable (since all received givinostat 100 mg b.i.d.). Additionally, concentration data for ITF2375 (Cycle 1 Day 28) in the 50 mg b.i.d. dose group was not available for PK analysis.

Measure: Assessment of Tlast of Givinostat and Metabolites (ITF2374 and ITF2375) in Part B of the Study

Time: Blood samples were collected in Part B on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 2 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of AUClast following administration of givinostat for 2 cycles in Part B. PK calculations were performed by standard non-compartmental analysis and AUClast was calculated using the linear trapezoidal rule. Following definition of the MTD in Part A, during Part B Cycle 1, givinostat was administered at 100 mg b.i.d. and during Part B Cycle 2 was administered at 100 mg, 75 mg and 50 mg b.i.d. (since dose reductions due to TEAEs were allowed from Cycle 2 onwards, as per protocol). Results are reported for Cycle 1 Day 1 and Cycle 2 Day 28 for the for the doses administered during Part B. Note: PK evaluation for the givinostat 75 mg and 50 mg b.i.d. dose groups for Cycle 1 Day 1 was not applicable (since all received givinostat 100 mg b.i.d.). Additionally, concentration data for ITF2375 (Cycle 1 Day 28) in the 50 mg b.i.d. dose group was not available for PK analysis.

Measure: Assessment of AUClast of Givinostat and Metabolites (ITF2374 and ITF2375) in Part B of the Study

Time: Blood samples were collected in Part B on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 2 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

Description: PK evaluation of givinostat and metabolites (ITF2374 and ITF2375) by assessment of AUC0-12 following administration of givinostat for 2 cycles in Part B. PK calculations were performed by standard non-compartmental analysis and AUClast was calculated using the linear trapezoidal rule. Following definition of the MTD in Part A, during Part B Cycle 1, givinostat was administered at 100 mg b.i.d. and during Part B Cycle 2 was administered at 100 mg, 75 mg and 50 mg b.i.d. (since dose reductions due to TEAEs were allowed from Cycle 2 onwards, as per protocol). Results are reported for Cycle 1 Day 1 and Cycle 2 Day 28 for the doses administered during Part B. Note: PK evaluation for the givinostat 75 mg and 50 mg b.i.d. dose groups for Cycle 1 Day 1 was not applicable (since all received givinostat 100 mg b.i.d.). Additionally, concentration data for ITF2374 (Cycle 1 Day 28) across all dose groups and for ITF2375 in the 50 mg b.i.d. dose group was not available for PK analysis.

Measure: Assessment of AUC0-12 of Givinostat and Metabolites (ITF2374 and ITF2375) in Part B of the Study

Time: Blood samples were collected in Part B on Cycle 1 Day 1: pre-dose and 2, 3 and 8 hours post-dose; and on Cycle 2 Day 28: pre-dose and 1, 2, 4 and 8 hours post-dose.

23 Hydroxyurea in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a serious and eventually fatal disease damaging the lungs and the heart. It results from narrowing and eventual blockage of small blood vessels in the lung, due to abnormal proliferation of cells in the blood vessel (arterial). Patients with PAH suffer from fatigue, shortness of breath, low oxygen levels, blood clots and heart failure. No therapies reverse the disease process in the lung arteries, however there are three approved drugs that can temporarily dilate the vessels and improve symptoms. However, all three drugs have significant side effects and toxicities, they do not work effectively in many patients, survival remains on average only 2 to 3 years once symptoms begin, and none of these drugs prevent the underlying disease process in the small arteries of the lung. PAH is known to develop in patients with a pre-existing class of bone marrow diseases called myeloproliferative disorders (MPDs). We and others have recently shown that patients with PAH have bone marrow changes similar to those seen in patients with MPDs, even without other signs and symptoms of those bone marrow diseases such as anemia or high platelet and white blood cell counts. Compared to healthy volunteers, patients with PAH have a higher frequency of immature stem and progenitor cells able to produce blood cells and vascular wall cells in their bone marrow. They also have higher circulating numbers of these cells in the blood, and increased localization of these cells in the lung blood vessels. When immature bone marrow cells from PAH patients and normal volunteers were infused into mice, the mice receiving PAH marrow cells developed similar lung and heart problems to PAH patients, suggesting that the bone marrow problem is a primary cause of the lung problems, and that the increased numbers of immature bone marrow cells in the bone marrow and blood of PAH patients causes the lung blood vessel disease. The drug hydroxyurea is used to inhibit the abnormally high level of bone marrow cell proliferation in patients with MPDs. It has been shown to reduce the numbers of circulating immature bone marrow cells in patients with MPDs. Hydroxyurea has been available for almost fifty years, and has been used to treat patients with MPDs, sickle cell anemia, and congenital heart disease for very prolonged periods of time, up to twenty or more years in individual patients. It has an excellent long-term safety profile and few side effects and is generally well tolerated. It does not appear to result in an increased rate of leukemia even with many years of treatment. In the current protocol, we hypothesize that treating patients with PAH with hydroxyurea will decrease the level of circulating immature bone marrow cells and interrupt the abnormal narrowing and occlusion of lung arteries. We will treat patients with moderately severe primary (no known underlying cause) PAH with 6 months of hydroxyurea, carefully monitoring side effects and adjusting dosage as necessary, and measure the effect on circulating immature cells, lung blood vessel pressures, other blood markers of active PAH, and exercise tolerance.

NCT01950585 Pulmonary Hypertension Drug: Hydroxyurea
MeSH: Hypertension, Pulmonary Familial Primary Pulmonary Hypertension Hypertension
HPO: Hypertension Pulmonary arterial hypertension

- HIV positivity - Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy, or that death within 30 days is likely - Presence of 9;22 BCR/ABL translocation as detected by conventional bone marrow cytogenetics or PCR for BCR/ABL transcript, or presence of JAK2 V617F mutation in bone marrow or peripheral blood cells. --- V617F ---

Primary Outcomes

Measure: The change in concentration of CD34+ circulating progenitors from baseline to 6 months (24 weeks (+/- 7 days)) on hydroxyurea.

Time: ongoing

24 Effects of Sympathicomimetic Agonists on the Disease Course and Mutant Allele Burden in Patients With JAK2-mutated Myeloproliferative Neoplasms. A Multicenter Phase II Trial.

The aim of this phase II study is to test a novel concept in the treatment of patients with myeloproliferative neoplasms (MPN), a disease of the bone marrow. With no current cure available, MPN are a group of chronic leukemias (blood cancers) in which patients produce too many blood cells. These increased blood cell numbers cause problems to the patient such as bleedings or thrombosis and some patients may progress to acute leukemia, a life threatening condition. Most MPN patients have a gene mutation called JAK2-V617F. The disease is maintained by mutant MPN stem cells that reside in the bone marrow in specialized locations called "niches". These niches need connections to the nervous system. New findings show that these connections are destroyed by the presence of the mutated MPN stem cells. Research teams found that some drugs (beta3-sympathicomimetics) can restore these damaged niches and at the same time reduce the MPN disease manifestation in a mouse model of MPN. Such sympathicomimetic drugs are already being used to treat patients with asthma or hyperactive bladder. These drugs have shown to have only few side effects. The study tests the effects of the beta-3-sympathicomimetic drug Mirabegron (Betmiga®) on MPN disease in 39 patients that carry a JAK2-V617F mutation. The hypothesis is that Mirabegron will have a beneficial effect on bone marrow niche cells and will thereby improve the disease manifestation in MPN patients. This study should provide a rapid answer whether targeting the nervous system of the niche cells could be useful for patients with MPN and warrants to be tested in larger and more long-term studies.

NCT02311569 Myeloproliferative Neoplasm Primary Myelofibrosis Essential Thrombocythemia Polycythemia Vera Drug: Mirabegron
MeSH: Polycythemia Vera Primary Myelofibrosis Polycythemia Myeloproliferative Disorders Thrombocytosis Thrombocythemia, Essential Neoplasms
HPO: Myeloproliferative disorder Neoplasm Polycythemia Thrombocytosis

Most MPN patients have a gene mutation called JAK2-V617F. --- V617F ---

The study tests the effects of the beta-3-sympathicomimetic drug Mirabegron (Betmiga®) on MPN disease in 39 patients that carry a JAK2-V617F mutation. --- V617F ---

Patients are defined as success for this endpoint, if they show a reduction of the JAK2-V617F allelic burden of 50% or more 24 weeks ± 4 weeks after registration when compared to baseline, and if they did not start a new MPN treatment before. --- V617F ---

Reduction in the burden of mutated alleles of ≥25% at 24 weeks (Red-25@24): Patients are defined as success for the Red-25@24 endpoint, if they show a reduction of the Jak2-V617F allelic burden of 25% or more 24 weeks ± 4 weeks after registration when compared to baseline, and if they did not start a new MPN treatment before. --- V617F ---

Reduction in the burden of mutated alleles of ≥25% at 12 weeks (Red-25@12) defined in the same way as the Red-25@24 endpoint, but evaluated at 12 weeks ± 4 weeks after registration.. Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of JAK2-V617F positive ET, PV or PMF at primary diagnosis or pretreated - JAK2-V617F mutant allele burden > 20% in the peripheral blood at study entry - Patient must give written informed consent before registration - WHO performance status 0-2 - Age ≥ 18 years - Adequate hematological values: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/ L - Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT/AP ≤ 2.5 x ULN - Adequate renal function (calculated creatinine clearance > 50 mL/min, according to the formula of Cockcroft-Gault) - Women are not breastfeeding. --- V617F ---

Reduction in the burden of mutated alleles of ≥25% at 12 weeks (Red-25@12) defined in the same way as the Red-25@24 endpoint, but evaluated at 12 weeks ± 4 weeks after registration.. Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of JAK2-V617F positive ET, PV or PMF at primary diagnosis or pretreated - JAK2-V617F mutant allele burden > 20% in the peripheral blood at study entry - Patient must give written informed consent before registration - WHO performance status 0-2 - Age ≥ 18 years - Adequate hematological values: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/ L - Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT/AP ≤ 2.5 x ULN - Adequate renal function (calculated creatinine clearance > 50 mL/min, according to the formula of Cockcroft-Gault) - Women are not breastfeeding. --- V617F --- --- V617F ---

Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of JAK2-V617F positive ET, PV or PMF at primary diagnosis or pretreated - JAK2-V617F mutant allele burden > 20% in the peripheral blood at study entry - Patient must give written informed consent before registration - WHO performance status 0-2 - Age ≥ 18 years - Adequate hematological values: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/ L - Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT/AP ≤ 2.5 x ULN - Adequate renal function (calculated creatinine clearance > 50 mL/min, according to the formula of Cockcroft-Gault) - Women are not breastfeeding. --- V617F ---

Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of JAK2-V617F positive ET, PV or PMF at primary diagnosis or pretreated - JAK2-V617F mutant allele burden > 20% in the peripheral blood at study entry - Patient must give written informed consent before registration - WHO performance status 0-2 - Age ≥ 18 years - Adequate hematological values: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/ L - Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT/AP ≤ 2.5 x ULN - Adequate renal function (calculated creatinine clearance > 50 mL/min, according to the formula of Cockcroft-Gault) - Women are not breastfeeding. --- V617F --- --- V617F ---

Three genes are frequently mutated in MPN and are implicated to be the phenotypic driver mutations: more than 95% of PV patients carry a somatic JAK2-V617F mutation, while about half of the remaining PV patients (2-3%) display mutations in JAK2 exon 12. Thus, almost all patients with PV have somatic mutations in the JAK2 gene. --- V617F ---

The mutational profiles of ET and PMF are more diverse: JAK2-V617F is found in 50-60% of the patients, whereas the recently described mutations in calreticulin (CALR) occur in 20-25% of the patients. --- V617F ---

Ruxolitinib, recently approved for PMF with splenomegaly, is effective in reducing spleen size and improving quality of life, but has little effect on the JAK2-V617F mutant allele burden and has so far not been reported to induce remissions. --- V617F ---

Furthermore, in a mouse model of MPN expressing the human JAK2-V617F mutation, this effect was found to be caused by early glial and sympathetic nerve damage and apoptosis of nestin+ MSCs triggered by the mutant HSCs. --- V617F ---

Mice with JAK2-V617F driven MPN treated with a beta-3-sympathicomimetic agonist not only restored nestin+ MSCs numbers, but also showed correction of thrombocytosis, neutrophilia, and bone marrow fibrosis, and efficiently reduced mutant hematopoietic progenitor numbers in bone marrow and peripheral blood. --- V617F ---

Primary Outcomes

Description: Primary endpoint of the trial is reduction in the burden of mutated alleles of ≥50% at 24 weeks (Red-50@24). Patients are defined as success for this endpoint, if they show a reduction of the JAK2-V617F allelic burden of 50% or more 24 weeks ± 4 weeks after registration when compared to baseline, and if they did not start a new MPN treatment before. All other evaluable patients will be considered as failures for this endpoint.

Measure: Reduction in the burden of mutated alleles of ≥50% at 24 weeks.

Time: at 24 weeks

Secondary Outcomes

Description: Reduction in the burden of mutated alleles of ≥50% at 12 weeks (Red-50@12) defined in the same way as the primary endpoint, but evaluated at 12 weeks ± 4 weeks after registration.

Measure: Reduction in the burden of mutated alleles of ≥50%

Time: at 12 weeks

Description: Reduction in the burden of mutated alleles of ≥25% at 24 weeks (Red-25@24): Patients are defined as success for the Red-25@24 endpoint, if they show a reduction of the Jak2-V617F allelic burden of 25% or more 24 weeks ± 4 weeks after registration when compared to baseline, and if they did not start a new MPN treatment before. All other evaluable patients will be considered as failures for this endpoint.

Measure: Reduction in the burden of mutated alleles of ≥25%

Time: at 24 weeks

Description: Reduction in the burden of mutated alleles of ≥25% at 12 weeks (Red-25@12) defined in the same way as the Red-25@24 endpoint, but evaluated at 12 weeks ± 4 weeks after registration.

Measure: Reduction in the burden of mutated alleles of ≥25%

Time: at 12 weeks

25 Phase II Study of P1101 in Early Myelofibrosis

This pilot phase II trial studies P1101 (polyethyleneglycol [PEG]-proline-interferon alpha-2b) in treating patients with myelofibrosis. PEG-proline-interferon alpha-2b is a substance that can improve the body's natural response and may slow the growth of myelofibrosis.

NCT02370329 Primary Myelofibrosis Secondary Myelofibrosis Other: Laboratory Biomarker Analysis Biological: PEG-Proline-Interferon Alfa-2b Other: Quality-of-Life Assessment
MeSH: Primary Myelofibrosis

To evaluate the impact of P1101 on bone marrow and histological features of myelofibrosis including cytogenetics, blast percentage, fibrosis, and JAK2-V617F allele burden by cohort (early vs intermediate-2/high risk). --- V617F ---

Primary Outcomes

Description: The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Measure: Best overall response (CR, PR, or CI) as determined by International Working Group Criteria

Time: Up to 3 years

Secondary Outcomes

Description: The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Measure: Incidence of adverse events, as measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4)

Time: Up to 3 years

Description: The distribution of survival time will be estimated using the method of Kaplan-Meier.

Measure: Survival time

Time: Time from registration to death due to any cause, assessed up to 3 years

Other Outcomes

Description: Patient-reported symptoms and QOL will be described at each time point using the mean, confidence interval, median, and range. Changes in individual symptoms, changes in a symptom scale composed of symptoms specific to MF patients, and changes in the MPN TSS will be investigated. Graphical procedures will include stream plots of individual patient scores and plots of average values over time. Correlational analyses will be done to determine the relationships among patients-reported symptoms and QOL, as well as with clinical outcomes and clinician-assessed symptoms.

Measure: Changes in patient-reported symptoms and QOL as measured by MPN-SAF

Time: Baseline to up to 3 years

26 Molecular Disease Profile of Haematological Malignancies. A Prospective Registry Study by the Rete Ematologica Lombarda (REL) Clinical Network

In this prospective multicentric study, the University of Pavia together with the Fondazione IRCCS Policlinico San Matteo, Pavia and the IRCCS Fondazione Maugeri, Pavia, Italy will provide a systematic analysis of gene mutations in hematological malignancies by using NGS techniques. Patients with a conclusive diagnosis of haematological malignancies according to WHO criteria referred to the Rete Ematologica Lombarda clinical network (REL, www.rel-lombardia.net) will be enrolled. The investigators will analyse genomic DNA extracted from hematopoietic cells at different time points of patient disease. The study contemplates the use of molecular platforms (Next Generation Sequencing, NGS) aimed at the identification of recurrent mutations in myeloid and lymphoid neoplasms, respectively. Screening of gene mutations by NGS will be prospectively implemented in the context of REL clinical network. Patient samples will be analyzed at diagnosis and sequentially during the course of the disease at specific timepoints. The researchers will analyze the correlations between somatic mutations, specific clinical phenotypes (according to the WHO classification) and disease evolution. This will allow to: 1) identify new recurrent genetic mutations involved in the molecular pathogenesis of hematological malignancies; 2) define the role of mutated genes, distinguishing between genes which induce a clonal proliferation of hematopoietic stem cells, and genes which determine the clinical phenotype of the disease; 3) identify mutations which are responsible for disease evolution; 4) define the diagnostic/prognostic role of the identified mutations, and update the current disease classifications and prognostic scores by including molecular parameters. A systematic biobanking of biological material will be provided.

NCT02459743 Hematological Malignancies
MeSH: Neoplasms
HPO: Neoplasm

In 2005 the University of Pavia described the diagnostic and prognostic significance of the JAK2 V617F mutation in myeloproliferative neoplasms (MPN): this mutation was included into the WHO classification of MPN and innovative anti-JAK2 drugs were developed. --- V617F ---

Primary Outcomes

Measure: Cumulative incidence of gene mutations in principal clone and subclones in each hematological malignancy

Time: 3 years

Secondary Outcomes

Measure: Genotype-phenotype correlations between clinical characteristics and mutational status

Time: 3 years

Measure: Overall survival and disease-free survival according to clinical and biological risk factors at diagnosis and during disease evolution

Time: 3 years

27 Ruxolitinib in Combination With High Dose Therapy and Autologous Stem Cell Transplantation for Myelofibrosis

To determine the safety of the approach of giving RUXOLITINIB before and after an autologous stem cell transplant, as measured by graft failure or death.

NCT02469974 Myelofibrosis MF Drug: RUXOLITINIB / INC 424 Drug: Filgrastim Drug: Busulfan
MeSH: Primary Myelofibrosis

Changes in Jak 2 V617F allele burden when present will be measured by quantitative RT-PCR. --- V617F ---

Primary Outcomes

Description: Safety of this approach as measured by graft failure or death

Measure: Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death

Time: 2 years

Secondary Outcomes

Description: Total CD34+ cell dose will be calculated based on results of flow cytometric analysis and patient's weight.

Measure: CD34 cells

Time: 4 years

Measure: The regimen related mortality (RRM)

Time: day 100

Measure: The regimen related mortality (RRM)

Time: day 365

Measure: Rate of engraftment/graft failure

Time: 4 years

Measure: Time of engraftment for neutrophils and platelets

Time: 4 years

Measure: The incidence of serious infectious complications

Time: up to 1 year post transplant

Description: The myelofibrosis score will be assessed as per the European Consensus Grading published by Thiele Grading Description at 365 days as compared to 180 days

Measure: Changes in marrow fibrosis score

Time: at 180 and 365 days post-transplant

Description: Changes in FISH abnormalities when present will be measured by cytogenetics.

Measure: Change in FISH allele

Time: at 365 days post-transplant

Description: Changes in Jak 2 V617F allele burden when present will be measured by quantitative RT-PCR

Measure: Change in JAK allele

Time: at 365 days post-transplant

Description: Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease

Measure: Rate of response

Time: at 6 months post-transplant

Description: Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease

Measure: Rate of response

Time: at 1 year post-transplant

28 A Phase 1 Study of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma

This is a Phase I, open-label, dose escalation and dose expansion study with a BID oral dose of tazemetostat. Subjects will be screened for eligibility within 14 days of the planned first dose of tazemetostat. A treatment cycle will be 28 days. Response assessment will be evaluated after 8 weeks of treatment and subsequently every 8 weeks while on study. The study has two parts: Dose Escalation and Dose Expansion. Dose escalation for subjects with the following relapsed/refractory malignancies: - Rhabdoid tumors: - Atypical teratoid rhabdoid tumor (ATRT) - Malignant rhabdoid tumor (MRT) - Rhabdoid tumor of kidney (RTK) - Selected tumors with rhabdoid features - INI1-negative tumors: - Epithelioid sarcoma - Epithelioid malignant peripheral nerve sheath tumor - Extraskeletal myxoid chondrosarcoma - Myoepithelial carcinoma - Renal medullary carcinoma - Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) (with Sponsor approval) - Synovial Sarcoma with a SS18-SSX rearrangement Dose Expansion at the MTD or the RP2D - Cohort 1 -(closed to enrollment) ATRT - Cohort 2 - MRT/RTK/selected tumors with rhabdoid features - Cohort 3 - INI-negative tumors: - Epithelioid sarcoma - Epithelioid malignant peripheral nerve sheath tumor - Extraskeletal myxoid chondrosarcoma - Myoepithelial carcinoma - Renal medullary carcinoma - Chordoma (poorly differentiated or de-differentiated) - Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval - Cohort 4 -(closed to enrollment) Tumor types eligible for Cohorts 1 through 3 or synovial sarcoma with SS18-SSX rearrangement

NCT02601937 Rhabdoid Tumors INI1-negative Tumors Synovial Sarcoma Malignant Rhabdoid Tumor of Ovary Drug: Tazemetostat
MeSH: Sarcoma Sarcoma, Synovial Rhabdoid Tumor Neoplasms
HPO: Neoplasm Sarcoma Soft tissue sarcoma Synovial sarcoma

JAK2 V617F) observed in cytogenetic testing and DNA sequencing. --- V617F ---

Primary Outcomes

Description: The incidence and severity of treatment-emergent adverse events (AEs) qualifying as protocol-defined DLTs in Cycle 1 will guide establishment of the protocol defined RP2D and/or MTD

Measure: To determine the MTD or the RP2D (Dose Escalation)

Time: 1 cycle/28 days

Measure: Dose expansion: Number of subjects with objective response using disease appropriate standardized response criteria

Time: Assessed every 8 weeks for duration of study participation which is estimated to be 24 months

Secondary Outcomes

Measure: Dose escalation: Number of subjects with objective response using disease appropriate standardized response criteria

Time: Assessed every 8 weeks for duration of study participation which is estimated to be 24 months

Measure: Dose Expansion: Progression-free survival (PFS)

Time: At 24 and 56 weeks post treatment using Kaplan-Meier method

Measure: Dose Expansion: Overall Survival (OS)

Time: At 24 and 56 weeks post treatment using Kaplan-Meier method

Measure: Incidence of treatment-emergent adverse events as a measure of safety and tolerability

Time: Adverse events assessed from first dose through 30 days post last dose

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Cmax

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Tmax

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-t)

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-12)

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): t1/2

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): CL/F

Time: Day 15

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Vd/F

Time: Day 15

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Ka

Time: Day 15

Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Ctrough

Time: Day 1 of cycles 2, 3 and 4

29 A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma

This is a Phase II, multicenter, open-label, single arm, 2-stage study of tazemetostat 800 mg BID administered orally in continuous 28 day cycles. Screening of subjects to determine eligibility for the study will be performed within 21 days of the first planned dose of tazemetostat. Eligible subjects will be enrolled into one of fivecohorts based on tumor type: - Cohort 1 (Closed for enrollment): MRT, RTK, ATRT, or selected tumors with rhabdoid features, including small cell carcinoma of the ovary hypercalcemic type [SCCOHT], also known as malignant rhaboid tumor of the ovary [MRTO] - Cohort 2 (Closed for enrollment): Relapsed or refractory synovial sarcoma with SS18-SSX rearrangement - Cohort 3 (Closed for enrollment): Other INI1 negative tumors or any solid tumor with an EZH2 gain of function (GOF) mutation, including: epithelioid malignant peripheral nerve sheath tumor (EMPNST), extraskeletal myxoid chondrosarcoma (EMC), myoepithelial carcinoma, other INI1-negative malignant tumors with Sponsor approval (e.g., dedifferentiated chordoma) any solid tumor with an EZH2 GOF mutation including but not limited to Ewing's sarcoma and melanoma - Cohort 4 (Closed for enrollment): Renal medullary carcinoma (RMC) - Cohort 5 (Closed for enrollment): Epithelioid sarcoma (ES) - Cohort 6 (Closed for enrollment): Epithelioid sarcoma (ES) undergoing mandatory tumor biopsy - Cohort 7 (Opened for enrollment): Poorly differentiated chordoma (or other chordoma with Sponsor approval) Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study. Response assessment will be evaluated after 8 weeks of treatment and then every 8 weeks thereafter while on study.

NCT02601950 Malignant Rhabdoid Tumors (MRT) Rhabdoid Tumors of the Kidney (RTK) Atypical Teratoid Rhabdoid Tumors (ATRT) Selected Tumors With Rhabdoid Features Synovial Sarcoma INI1-negative Tumors Malignant Rhabdoid Tumor of Ovary Renal Medullary Carcinoma Epithelioid Sarcoma Poorly Differentiated Chordoma (or Other Chordoma With Sponsor Approval) Any Solid Tumor With an EZH2 GOF Mutation Drug: Tazemetostat
MeSH: Sarcoma Sarcoma, Synovial Rhabdoid Tumor Chordoma Carcinoma, Medullary Kidney Neoplasms Neoplasms
HPO: Chordoma Neoplasm Renal neoplasm Sarcoma Soft tissue sarcoma Synovial sarcoma

JAK2 V617F) observed in cytogenetic testing and DNA sequencing. --- V617F ---

Primary Outcomes

Measure: Number of subjects with objective response using disease appropriate standardized response criteria

Time: Assessed every 8 weeks for duration of study participation which is estimated to be 24 months

Description: The number of subjects with CR, PR, or stable disease (SD) at 16 week assessment

Measure: Progression-free survival (PFS) rate for Cohort 2 (Relapsed/Refractory Synovial Sarcoma)

Time: 16 weeks of treatment

Measure: Assess the effects of tazemetostat on tumor immune priming for Cohort 6

Time: Through study completion, an average of 2 years

Secondary Outcomes

Measure: Duration of response in subjects in Cohorts 1, 2, 3, 4, 5, 6 and 7 and in Cohorts 1, 3, 4, 5, 6 and 7 combined for subjects achieving a complete response (CR) and partial response (PR) following oral administration of tazemetostat 800 mg BID

Time: Assess every 8 weeks for duration of study participation which is estimated to be 24 months

Description: The number of subjects with confirmed CR, PR or SD at 32 week assessment

Measure: Disease control rate (DCR) in subjects with epithelioid sarcoma (Cohort 5) and epithelioid sarcoma undergoing mandatory biopsy (Cohort 6) following oral administration of tazemetostat 800 mg BID

Time: 32 weeks of treatment

Description: ORR (confirmed CR+PR, RECIST 1.1)

Measure: Overall response rate ORR for Cohort 2 (relapsed/refractory synovial sarcoma) and Cohort 6 (epithelioid sarcoma undergoing mandatory biopsy)

Time: Assessed every 8 weeks for duration of study participation which is estimated to be 24 months

Description: The time from date of first dose of study treatment to the earlier of the date of first documented disease progression or date of death due to any cause

Measure: PFS for each cohort

Time: 24, 32 and 56 weeks of treatment

Description: The time from the date of the first dose of study treatment to the date of death due to any cause

Measure: OS for each cohort

Time: 24, 32 and 56 weeks of treatment

Measure: Incidence of treatment-emergent adverse events as a measure of safety and tolerability

Time: Adverse events assessed from first dose through 30 days post last dose

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): Cmax

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): Tmax

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): AUC(0-t)

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): AUC(0-12)

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): t1/2

Time: Days 1 and 15

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): CL/F

Time: Days 1, 15, 29, 43, and 57

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): Vd/F

Time: Days 1, 15, 29, 43, and 57

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): Ka

Time: Days 1, 15, 29, 43, and 57

Measure: Pharmacokinetics profile of tazemetotstat and its metabolite (plasma): Ctrough

Time: Days 29, 43 and 57

Description: IHC assessments of changes in the level of H3K27-Me3 following tazemetostat dosing

Measure: Investigate the pharmacodynamics (PD) effects of tazemetostat in tumor tissue

Time: At week 8

30 Risk Factors for Variceal Bleeding in Egyptian Patients With Non-Cirrhotic Portal Hypertension

Background & Aims: Non-cirrhotic portal hypertension (NCPH) represents a relatively infrequent group of conditions. This work aimed at determining causes of NCPH and evaluating the role of some clinical, laboratory, imaging and endoscopic parameters in prediction of variceal bleeding in an Egyptian cohort with NCPH. Methods: Sixty patients with non-cirrhotic portal hypertension and oesophageal varices were included. All underwent complete clinical evaluation, laboratory investigations, Color Doppler ultrasonography, platelet count/spleen diameter (mm) ratio and upper gastrointestinal endoscopy. Patients were classified into two groups according to variceal bleeding: (1) Group I: twenty six patients with history of bleeding or had an attack of bleeding during one year follow-up; and (2) Group II: thirty four patients without bleeding.

NCT02635815 Portal Hypertension Procedure: Upper gastrointestinal endoscopy
MeSH: Hypertension, Portal Hypertension
HPO: Hypertension Portal hypertension

It was done only for patients with Budd-Chiari syndrome and extrahepatic portal vein thrombosis: anticardiolipin antibodies, lupus anticoagulant, antinuclear antibodies, protein C, S, antithrombin III, factor V Leiden G1691A mutation, prothrombin gene G20210A mutation, methylene tetrahydrofolate reductase C677T mutation by PCR, Janus tyrosine kinase-2 (JAK II) V617F mutation by PCR (to exclude myeloproliferative disorders) and flow cytometry for CD55 and CD59 (to exclude paroxysmal nocturnal hemoglobinuria); (4) Abdominal ultrasonography: for liver size, echogenicity, spleen size, portal vein diameter and ascites; (5) Color Doppler ultrasonographic study: was done in the morning after an overnight fasting using a color Doppler unit with a 3.5 MHz convex probe for confirmation of portal vein (PV) patency and diameter, mean PV flow velocity (mean PVV) (cm/sec), PV direction of flow, splenic vein patency and diameter, presence of portosystemic collaterals and patency of hepatic veins; (6) Platelet count/spleen diameter ratio: calculated as: platelet count/ maximum spleen bipolar diameter by ultrasound in mm; (7) Ultrasonography guided liver biopsy: for diagnosis of NCPH and exclusion of cirrhotic portal hypertension; and (8) Upper gastrointestinal endoscopy using the Pentax video endoscope EG 3440. --- G1691A --- --- G20210A --- --- C677T --- --- V617F ---

Primary Outcomes

Measure: The presence or absence of variceal bleeding within one year of follow up.

Time: 1 year

31 A Phase II Single-Arm Study of the Efficacy and Safety of Oral Rigosertib in Patients With Myelofibrosis (MF) and Anemia

The goal of this clinical research study is to learn if rigosertib can help to control MF in patients with anemia. The safety of this drug will also be studied. This is an investigational study. Rigosertib is not FDA-approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. Up to 35 participants will be enrolled in this study. All will be enrolled at MD Anderson.

NCT02730884 Leukemia Myelofibrosis Anemia Splenomegaly Drug: Rigosertib Behavioral: Questionnaire
MeSH: Anemia Primary Myelofibrosis Splenomegaly
HPO: Anemia Splenomegaly

Measurement of JAK2 V617F allele burden in BM samples, if not done within 6 months prior to Screening, must be provided with the Screening BM biopsy/aspirate report (patients are eligible regardless of JAK2 mutation status); 3. Anemia or RBC-transfusion dependence defined as follows: a) Anemia: defined for the purpose of this protocol as 1) a hemoglobin level <10 g/L on every determination over 84 days before study-entry, without RBC-transfusions, or 2) a hemoglobin level <10 g/L on a patient that is receiving RBC-transfusions periodically but not meeting criteria for transfusion-dependent patient as defined below. --- V617F ---

Primary Outcomes

Description: Spleen response defined as ≥ 35% spleen volume reduction from Baseline, which must be confirmed by MRI or CT measurement per revised International Working Group for Myelofibrosis Research and Treatment (IWG MRT) response criteria.

Measure: Change in Spleen Volume

Time: Baseline and 48 weeks

Description: Anemia response defined as the proportion of transfusion-independent patients with Hgb increase of at least 2 g/dL from Baseline or the proportion of transfusion-dependent patients becoming transfusion independent for at least 12 weeks as defined in 2013 International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria.

Measure: Change in Anemia Response

Time: Baseline and 48 weeks

Secondary Outcomes

Description: Symptoms response defined as the proportion of patients achieving ≥ 50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) at any time before Week 48.

Measure: Symptoms Response

Time: 48 weeks

32 Assessment of the Prevalence of Major Psychiatric Disorders in a Cohort of Women With Clinical Criteria Corresponding to Pure, Abortive-form, Obstetrical, Antiphospholipid Syndrome

The primary objective of this study was to evaluate and compare the prevalence of the following psychiatric pathologies (based on the MINI5.0.0 questionnaire) among 3 groups of women (Leiden versus aP1Ab-positive versus thrombophilia-negative) with similar obstetrical histories 10 years after their initial assessment/diagnosis. - Mood disorders, including depressive episodes during the previous two weeks, recurrent depressive disorders at any point in life, dysthymia in the last two years, or any current or past manic episode; - Anxiety disorders, including current agoraphobia, current panic disorders, agoraphobia with panic disorders, current social phobia, generalized anxiety in the last 6 months, or current posttraumatic stress syndrome; - Apparent psychotic syndromes, including isolated or recurrent psychotic syndromes, past or present (clinically validated), - Current alcohol or drug problems (dependence or abuse).

NCT02833194 Antiphospholipid Syndrome Factor V Leiden Thrombophilia
MeSH: Thrombophilia Antiphospholipid Syndrome Syndrome Mental Disorders Problem Behavior
HPO: Behavioral abnormality Hypercoagulability

Exclusion Criteria: - Any history of thrombotic events or any treatment given during previous pregnancies that might have modified the natural course of the condition - Women whose pregnancy losses could be explained by infectious, metabolic, anatomic or hormonal facotrs, or associated with paternal or maternal chromosomal causes - Seropositivity for HIV, hepatitis B or C - Women with antithrombin, protein C, or protein S deficiency, and women with abnormal fibrinogen or with the JAK2 V617F mutation were further excluded. --- V617F ---

Primary Outcomes

Measure: Mini Internationl Neuropsychiatric Interview 5.0.0

Time: 10 years

33 The Prognostic Value of PGF and sFlt1 Variations Induced by the First Low-molecular-weight-heparin Injections in Women With Obstetrical Antiphospholipids Antibody Syndrome Starting a New Pregnancy and Following Treatment in Accordance With International Recommendations

The primary objective of this study is to evaluate plasmatic concentrations of free PGF and sFlt1 for blood samples taken before a first low-molecular-weight-heparin injection and also for blood samples taken on the 4th day of injections (the latter correspond to the first systematic control of platelet counts) in women who have an obstetric antiphospholipid antibody syndrome and who are initiating a new pregnancy with recommended treatment. Our goal is to test the prognostic value of these data on the occurrence of: - pregnancy loss categorized as embryonic loss (before 10 weeks gestation), fetal death (before 20 weeks gestation), stillbirths (from 20 weeks gestation to delivery), and neonatal death defined before reaching 28 days of age. - ischemic placental pathology (pre-eclampsia, retro-placental hematoma, birth of a small-for-gestational-age infant)

NCT02855047 Antiphospholipid Syndrome
MeSH: Antiphospholipid Syndrome Syndrome

- Women in the APS subgroup: persistently positive for LA, and/or aCL and/or aBeta2GP1 - Women initiating a new pregnancy during the 18 month observational period after obstetric APS diagnosis Exclusion Criteria: - Any history of thrombotic events or any treatment given during previous pregnancies that might have modified the natural course of the condition - Women whose pregnancy losses could be explained by infectious, metabolic, anatomic or hormonal factors, or associated with paternal or maternal chromosomal causes - Seropositivity for HIV, hepatitis B or C - Women with antithrombin, protein C, or protein S deficiency, and women with abnormal fibrinogen or with the JAK2 V617F mutation were further excluded. --- V617F ---

Primary Outcomes

Description: The primary endpoint was a composite outcome that included any of the following events occurring after 19 completed weeks during the observed pregnancy: preeclampsia, abruptio placenta, or fetal growth restriction (< 10th percentile), summarized as the so-called placenta-mediated complications PMCs.

Measure: Presence/absence of at least one of the following: preeclampsia, abruptio placenta, or fetal growth restriction (< 10th percentile)

Time: 19 weeks gestation

34 Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS): Fundamental Observational in Vitro Study Using Samples From a Collection

Heat-shock proteins (HSP) have been very highly conserved throughout the evolution of species and are characterized by their chaperone function, thanks to their ability to prevent aggregation and to promote the renaturation/break down of damaged proteins. Among other targets, they also chaperone JAK2, a key step that is deregulated in signalling in myeloproliferative syndromes (MPS) because of the JAK2V617F mutation. These HSP also have a potent cytoprotective action through their multiples inhibiting effects on apoptotic processes. Little is known about levels of HSP expression, in particular for HSP70 and HSP27, in MPS cells. However, in vitro studies of different cell models have shown the interest of HSP90 inhibitors in slowing cell proliferation in MPS. These results have been confirmed in animal models with results in terms of blood counts and overall survival. In addition, it seems that the V617F mutated form of JAK2 is more sensitive than the wild-type to HSP90 inhibitors. Finally, inhibitors of HSP90 remain efficacious with regard to the inhibition of cell growth, even in cases of resistance to JAK2 inhibitors. Nonetheless, HSP90 inhibitors are known to stimulate the expression of other HSP, notably HSP27 and HSP70, which are, through their properties, tumorigenic and could lead to an escape phenomenon. Thus the combined use of several HSP inhibitors could be beneficial, and eventually present synergistic effects on the inhibition of tumour processes.

NCT02873832 Myeloproliferative Syndrome Biological: Blood sample Other: Flow cytometry Other: western blot
MeSH: Myeloproliferative Disorders Syndrome
HPO: Myeloproliferative disorder

In addition, it seems that the V617F mutated form of JAK2 is more sensitive than the wild-type to HSP90 inhibitors. --- V617F ---

Primary Outcomes

Description: Level of protein expression using flow cytometry and western blot

Measure: Comparing the level of expression of HSP (HSP90, HSP70, HSP27) between cells from a collection of samples of patients with myeloproliferative disease and healthy controls .

Time: through study completion, an average of 1 year

Secondary Outcomes

Measure: Cell death after in vitro treatment with different HSP inhibitors

Time: through study completion, an average of 1 year

35 A Phase 1 Study of Ruxolitinib, Steroids and Lenalidomide for Relapsed/Refractory Multiple Myeloma (RRMM) Patients

This is a phase 1, multicenter, open-label study evaluating the safety and efficacy of ruxolitinib, steroids and lenalidomide among MM patients who currently show progressive disease.

NCT03110822 Multiple Myeloma Drug: Ruxolitinib Oral Tablet [Jakafi] Drug: Lenalidomide Drug: Methylprednisolone
MeSH: Multiple Myeloma Neoplasms, Plasma Cell
HPO: Multiple myeloma

The activating JAK2 V617F mutation results in uncontrolled cytokine and growth factor signaling, and is believed to play a key role in the pathophysiology of myeloproliferative neoplasms. --- V617F ---

Primary Outcomes

Description: MTD will be determined by measuring incidence of the dose-limiting toxicities (DLTs) per dose level, of ruxolitinib in combination with steroids and lenalidomide for MM patients currently with progressive disease.

Measure: Determination of maximum tolerated dose (MTD) of ruxolitinib in combination with steroids and lenalidomide [Tolerability].

Time: 30 months

Description: Safety will be measured by counting the occurrence of adverse events throughout the study, graded via Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria

Measure: Incidence of Treatment-Emergent Adverse Events [Safety]

Time: 54 months

Secondary Outcomes

Description: Overall response rate (ORR) is defined as CR + VGPR + PR

Measure: Overall response rate (ORR) as a measure of efficacy

Time: 54 months

Description: Clinical benefit rate is defined as ORR + MR

Measure: Clinical benefit rate (CBR) as a measure of efficacy

Time: 54 months

Description: Progression-free survival will be measured in months as the time from initiation of therapy to progressive disease or death from any cause, whichever occurs first

Measure: Progression Free Survival (PFS)

Time: 54 months

Description: Time to response, defined as the time from the initiation of therapy to the first evidence of confirmed clinical benefit defined as > minimal response (MR, including patients who achieved a complete response (CR), very good partial response (VGPR), partial response (PR), or MR

Measure: Assessment of the time to response as a measure of efficacy

Time: 54 months

Description: Duration of response, defined as the time (in months) from the first response to progressive disease

Measure: Assessment of the duration of response as a measure of efficacy

Time: 54 months

Description: Overall survival, defined as the time (in months) from initiation of therapy to death from any cause or last follow-up visit

Measure: Assessment of the overall survival (OR) as a measure of efficacy

Time: 54 months

Description: Response to initial therapy (ruxolitinib and methylprednisolone alone) will be compared to the response to therapy with addition of lenalidomide (ruxolitinib, lenalidomide, methylprednisolone)

Measure: Assessment of response in additional cohort

Time: 54 months

36 A Phase I Study of Single Agent Tazemetostat in Subjects With Advanced Solid Tumors and B-Cell Lymphomas With Hepatic Dysfunction

This phase I trial studies the best dose and side effects of tazemetostat in treating patients with solid tumors or B-cell lymphomas with liver dysfunction that have spread to other places in the body or cannot be removed by surgery. Tazemetostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

NCT03217253 Ann Arbor Stage III B-Cell Non-Hodgkin Lymphoma Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma Metastatic Malignant Solid Neoplasm Stage III Hepatocellular Carcinoma AJCC v7 Stage IIIA Hepatocellular Carcinoma AJCC v7 Stage IIIB Hepatocellular Carcinoma AJCC v7 Stage IIIC Hepatocellular Carcinoma AJCC v7 Stage IV Hepatocellular Carcinoma AJCC v7 Stage IVA Hepatocellular Carcinoma AJCC v7 Stage IVB Hepatocellular Carcinoma AJCC v7 Unresectable Solid Neoplasm Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Tazemetostat
MeSH: Lymphoma Carcinoma Lymphoma, Non-Hodgkin Carcinoma, Hepatocellular Lymphoma, B-Cell Neoplasms
HPO: B-cell lymphoma Carcinoma Hepatocellular carcinoma Lymphoma Neoplasm Non-Hodgkin lymphoma

JAK2 V617F) observed in cytogenetic testing and DNA sequencing - Has a prior history of T-acute lymphoblastic lymphoma (T-LBL)/T-acute lymphoblastic leukemia (ALL) Inclusion Criteria: - Patients must have histologically and/or cytologically confirmed solid tumors or B cell lymphoma that are metastatic or unresectable and for which standard treatment options do not exist; patients with hepatocellular carcinoma are eligible without pathological diagnosis if diagnosed on the basis of blood work and imaging - Patients with evaluable disease will be eligible - All patients must have completed any prior chemotherapy, targeted therapy and major surgery, >= 28 days before study entry; for daily or weekly chemotherapy without the potential for delayed toxicity, a washout period of 14 days may be acceptable, and questions related to this can be discussed with study principal investigator - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels - All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade =< 1 (except alopecia) at the time of enrollment - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >= 100,000/mcL - Hemoglobin >= 90 g/L (9.0 g/dL) - Creatinine within normal institutional limits OR calculated creatinine clearance >= 60 mL/min/1.73 --- V617F ---

JAK2 V617F) observed in cytogenetic testing and DNA sequencing - Has a prior history of T-acute lymphoblastic lymphoma (T-LBL)/T-acute lymphoblastic leukemia (ALL) Ann Arbor Stage III B-Cell Non-Hodgkin Lymphoma Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma Metastatic Malignant Solid Neoplasm Stage III Hepatocellular Carcinoma AJCC v7 Stage IIIA Hepatocellular Carcinoma AJCC v7 Stage IIIB Hepatocellular Carcinoma AJCC v7 Stage IIIC Hepatocellular Carcinoma AJCC v7 Stage IV Hepatocellular Carcinoma AJCC v7 Stage IVA Hepatocellular Carcinoma AJCC v7 Stage IVB Hepatocellular Carcinoma AJCC v7 Unresectable Solid Neoplasm Lymphoma Carcinoma Lymphoma, Non-Hodgkin Carcinoma, Hepatocellular Lymphoma, B-Cell Neoplasms PRIMARY OBJECTIVES: I. To determine safety, tolerability and recommended phase 2 dose (RP2D) of tazemetostat in patients with varying degrees of hepatic dysfunction. --- V617F ---

Primary Outcomes

Description: Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to study treatment.

Measure: Incidence of adverse events of tazemetostat in patients with varying degrees of hepatic dysfunction assessed using Common Terminology Criteria for Adverse Events version 5.0

Time: Up to 2 years

Description: RP2D will be determined.

Measure: Recommended phase 2 dose (RP2D) of tazemetostat in patients with varying degrees of hepatic dysfunction

Time: Up to 2 years

Secondary Outcomes

Description: Plasma concentrations will be measured by Q2 Solutions using a validated Liquid chromatography (LC)/mass spectrometry (MS)/MS assay. Molecular and clinical predictors of clinical outcomes will be investigated using logistic regression and Cox proportional hazards models. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships. Given the small sample size, and exploratory nature of these endpoints, all pharmacodynamic analyses conducted will be considered exploratory. All analyses will be considered exploratory and inference will be performed with appropriate caution.

Measure: Pharmacokinetic (PK) profiles of tazemetostat in patients with varying degrees of hepatic dysfunction

Time: Up to course 4 day 1 (day 85)

Description: Molecular and clinical predictors of clinical outcomes will be investigated using logistic regression and Cox proportional hazards models. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships. All analyses will be considered exploratory and inference will be performed with appropriate caution.

Measure: Antitumor activity of tazemetostat

Time: Up to 2 years

Description: Molecular and clinical predictors of clinical outcomes will be investigated using logistic regression and Cox proportional hazards models. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships. All analyses will be considered exploratory and inference will be performed with appropriate caution.

Measure: Antitumor activity of tazemetostat in population with tumors with aberrations in EZH2 or SWI/SNF complex pathways

Time: Up to 2 years

Description: Response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1

Measure: Objective confirmed response

Time: Up to 2 years

Description: Response will be assessed using the RECIST criteria 1.1.

Measure: Duration of response

Time: Up to 2 years

Description: Response will be assessed using the RECIST criteria 1.1.

Measure: Best response

Time: Up to 2 years

37 Genomic Screening for Hereditary Erythrocytosis and Related Diseases

Unexplained polycythemias are rare diseases, and therefore, the collection of data inherent to these diseases will not only improve their characterisation, but also allow stratification according to the risks and the course of the disease. The objective of this project is to constitute a database on the disease which will allow us to better understand it and in due course improve its management. The GENRED project thus bears uniquely on the collection of information, which will be gathered throughout the usual management of patients for this type of disease.

NCT03263364 Hereditary Erythrocytosis/Idiopathic Erythrocytosis
MeSH: Polycythemia
HPO: Polycythemia

The required tests are: complete blood counts - Blood electrolytes - Arterial and venous gazes - Serum erythropoietin dosage - Liver function tests - JAK2 mutations (both V617F and exon 12) - Bone marrow aspirate and/or biopsy and/or endogenous BFU-E culture - Abdominal ultrasound - Lung function tests Inclusion Criteria: The characteristics of the patients included in the database will be described in terms of numbers and percentages for qualitative variables and in terms of means and standard deviations or medians and interquartile intervals for quantitative variables. --- V617F ---

The required tests are: complete blood counts - Blood electrolytes - Arterial and venous gazes - Serum erythropoietin dosage - Liver function tests - JAK2 mutations (both V617F and exon 12) - Bone marrow aspirate and/or biopsy and/or endogenous BFU-E culture - Abdominal ultrasound - Lung function tests Hereditary Erythrocytosis/Idiopathic Erythrocytosis Polycythemia null --- V617F ---

Primary Outcomes

Measure: Germline mutations that cause Hereditary Erythrocytosis/Idiopathic Erythrocytosis

Time: at baseline

38 A Phase II Study of Tazemetostat (EPZ-6438) in Recurrent or Persistent Endometrioid or Clear Cell Carcinoma of the Ovary, and Recurrent or Persistent Endometrioid Endometrial Adenocarcinoma

This phase II trial studies how well tazemetostat works in treating patients with ovarian or endometrial cancer that has come back (recurrent). Drugs used in chemotherapy, such as tazemetostat, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

NCT03348631 FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma Recurrent Endometrial Endometrioid Adenocarcinoma Recurrent Ovarian Carcinoma Recurrent Ovarian Clear Cell Adenocarcinoma Recurrent Ovarian Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Other: Laboratory Biomarker Analysis Drug: Tazemetostat
MeSH: Carcinoma Adenocarcinoma Carcinoma, Endometrioid Adenocarcinoma, Clear Cell
HPO: Carcinoma

JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing - A prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL) - Severe, active co-morbidity per the treating investigator's discretion - Pregnant or lactating patients - Known human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with tazemetostat; in addition, treatments involved in this protocol may be immunosuppressive, increasing the risk of lethal infections in this patient population - Treatment with strong inhibitors or inducers of CYP3A within 14 days of registration and during the study treatment Inclusion Criteria: - Pathologically (histologically or cytologically) proven diagnosis of recurrent or persistent ovarian endometrioid or clear cell carcinoma, OR recurrent or persistent endometrioid endometrial adenocarcinoma; patients with recurrent endometrial cancer must have mismatch repair (MMR) immunohistochemistry completed; if they are found to be mismatch repair deficient, they should be offered treatment with immune checkpoint inhibition before consideration for treatment on trial; primary ovarian tumors must be at least 50% endometrioid or clear cell morphology, or have histologically documented recurrence with at least 50% endometrioid or clear cell morphology; institutional pathology reports must be provided indicating at least 50% endometrioid or clear cell morphology for ovarian tumors (primary or recurrent lesions) - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be > 15 mm in short axis when measured by CT or MRI - Patients must have had at least one, but no more than 3, prior cytotoxic regimens for management of primary disease; unlimited prior hormonal therapy, targeted therapy (including immunotherapy) or antiangiogenic therapy will be permitted - Patients must have completed prior therapy: - Chemotherapy: cytotoxic - At least 28 days since last dose of chemotherapy prior to registration. --- V617F ---

JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing - A prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL) - Severe, active co-morbidity per the treating investigator's discretion - Pregnant or lactating patients - Known human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with tazemetostat; in addition, treatments involved in this protocol may be immunosuppressive, increasing the risk of lethal infections in this patient population - Treatment with strong inhibitors or inducers of CYP3A within 14 days of registration and during the study treatment FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma Recurrent Endometrial Endometrioid Adenocarcinoma Recurrent Ovarian Carcinoma Recurrent Ovarian Clear Cell Adenocarcinoma Recurrent Ovarian Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Carcinoma Adenocarcinoma Carcinoma, Endometrioid Adenocarcinoma, Clear Cell PRIMARY OBJECTIVE: I. To assess the clinical activity (overall response rate) of tazemetostat in patients with recurrent or persistent endometrioid or clear cell ovarian carcinoma, and patients with recurrent or persistent endometrioid endometrial adenocarcinoma. --- V617F ---

Primary Outcomes

Measure: Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1

Time: Up to 6 months

Secondary Outcomes

Measure: Tumor response in patients with ARID1A mutations using tumor response as defined by RECIST v 1.1

Time: Up to 6 months

Measure: Incidence of adverse events according to grade of toxicity by organ or organ system

Time: Up to 5 years

Description: Will be characterized by quartiles and the median of the distribution with confidence intervals. Kaplan-Meier plots will show an estimate of the survival function for these populations.

Measure: Progression-free survival

Time: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years

Description: Will be characterized by quartiles and the median of the distribution with confidence intervals. Kaplan-Meier plots will show an estimate of the survival function for these populations.

Measure: Overall survival

Time: From study entry to time of death or the date of last contact, assessed up to 5 years

Other Outcomes

Description: Associations between BAF250a and ARID1A mutations may be examined with contingency table analysis (e.g. potentially including Chi-square analyses or Spearman's correlation).

Measure: ARID1A mutational status

Time: Up to 6 months

Description: Associations between BAF250a and ARID1A mutations may be examined with contingency table analysis (e.g. potentially including Chi-square analyses or Spearman's correlation).

Measure: BAF250a expression by immunohistochemistry

Time: Up to 6 months

39 Concomitant Ruxolitinib Induction and Maintenance With Cytarabine Based Chemotherapy in Secondary Acute Myelogenous Leukemia Evolving From Myeloproliferative Neoplasm

This trial aimed to investigate the therapeutic efficacy of ruxolitinib in combination with cytotoxic chemotherapy for post-myeloproliferative neoplasm secondary acute myeloid leukemia.

NCT03558607 Secondary Acute Myelogenous Leukemia Evolving From Myeloproliferative Disorder Drug: Ruxolitinib
MeSH: Leukemia Neoplasm Metastasis Leukemia, Myeloid Leukemia, Myeloid, Acute Myeloproliferative Disorders Neoplasms
HPO: Acute megakaryocytic leukemia Acute myeloid leukemia Leukemia Myeloid leukemia Myeloproliferative disorder Neoplasm

JAK2 V617F mutation, which is a hallmark of MPN, has been reported to be carried in approximately 35-50% of patients with post-MPN AML. --- V617F ---

Primary Outcomes

Measure: complete remission rate

Time: After 12 months from induction chemotherapy

Measure: complete remission with incompletre recovery rate

Time: After 12 months from induction chemotherapy

Secondary Outcomes

Description: from the date of transplantation to death from any cause

Measure: Overall survival

Time: 3, 6, 12, 24 months after induction chemotherapy

Description: from the date of transplantation to the date of disease progression or death from any cause

Measure: Progression-free survival

Time: 3, 6, 12, 24 months after induction chemotherapy

Description: according to CTCAE version 4.03

Measure: Toxicity profile

Time: 3, 6, 12, 24 months after induction chemotherapy

40 Arterial Function and Atherosclerosis in Patients With JAK2 V167F Positive Essential Thrombocythemia

The aim of the study is to examine (a) whether patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of arterial stiffness, pulse-wave velocity and coronary calcium score in a 4 year observation period, and (b) whether the burden of JAK2 V617F mutation correlates with the measured vascular parameters. All subjects will be examined twice. The first visit already took place between the years 2014 - 2015 and the second visit will take place between 2018-2019. All participants will have signed their informed consent before entering the study. Each visit will consist of completing a structured questionnaire (on personal and family medical history, risk factors for CVD and medication), physical examination, donating a blood sample for laboratory tests and undergoing carotid ultrasound and coronary calcium measurement oft the extent of coronary artery calcification. At the first and the second examination the JAK2 V617F allele burden, i.e. the percentage of mutated alleles, will be determined from genomic DNA in peripheral blood.

NCT03828422 Atherosclerosis Diagnostic Test: imaging
MeSH: Atherosclerosis Thrombocytosis Thrombocythemia, Essential
HPO: Atherosclerosis Thrombocytosis Type IV atherosclerotic lesion

Arterial Function and Atherosclerosis in Essential Thrombocythemia The aim of the study is to examine (a) whether patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of arterial stiffness, pulse-wave velocity and coronary calcium score in a 4 year observation period, and (b) whether the burden of JAK2 V617F mutation correlates with the measured vascular parameters. --- V617F ---

Arterial Function and Atherosclerosis in Essential Thrombocythemia The aim of the study is to examine (a) whether patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of arterial stiffness, pulse-wave velocity and coronary calcium score in a 4 year observation period, and (b) whether the burden of JAK2 V617F mutation correlates with the measured vascular parameters. --- V617F --- --- V617F ---

At the first and the second examination the JAK2 V617F allele burden, i.e. the percentage of mutated alleles, will be determined from genomic DNA in peripheral blood. --- V617F ---

Change of carotid artery stiffness (expressed by beta-stiffness index and pulse wave velocity) in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid artery stiffness (expressed as two interrelated parameters, the beta-stiffness index and the pulse wave velocity) in a 4 year observation period?. --- V617F ---

Change of carotid artery stiffness (expressed by beta-stiffness index and pulse wave velocity) in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid artery stiffness (expressed as two interrelated parameters, the beta-stiffness index and the pulse wave velocity) in a 4 year observation period?. --- V617F --- --- V617F ---

Change of carotid artery plaque score in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid plaque score in a 4 year observation period? --- V617F ---

Change of carotid artery plaque score in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid plaque score in a 4 year observation period? --- V617F --- --- V617F ---

Thus, the carotid plaque score ranges from 0 (absence of plaques, best) to 6 (plaques present in all segments on both sides, worst outcome).. Change of coronary calcium burden in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of coronary calcium score in a 4 year observation period?. --- V617F ---

Thus, the carotid plaque score ranges from 0 (absence of plaques, best) to 6 (plaques present in all segments on both sides, worst outcome).. Change of coronary calcium burden in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of coronary calcium score in a 4 year observation period?. --- V617F --- --- V617F ---

Change of digital endothelial function, expressed as the Reactive Hyperemia Index, in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show greater changes digital endothelial function, expressed as the Reactive Hyperemia Index (RHI), in a 4 year observation period? --- V617F ---

Change of digital endothelial function, expressed as the Reactive Hyperemia Index, in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.. Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show greater changes digital endothelial function, expressed as the Reactive Hyperemia Index (RHI), in a 4 year observation period? --- V617F --- --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F --- --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F --- --- V617F --- --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F --- --- V617F --- --- V617F --- --- V617F ---

RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).. Association of the JAK2 V617F mutation burden with the coronary calcium burden.. Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.. Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Inclusion Criteria: - patients with JAK2 V617F positive essential thrombocythemia - age-and sex-matched apparently healthy control subjects Exclusion Criteria: - personal history of any atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke) - chronic kidney disease stage 3 and above - known cancer - chronic inflammatory disease - autoimmune disease - pregnancy Atherosclerosis Atherosclerosis Thrombocytosis Thrombocythemia, Essential 1. Patients and control subjects Patients are selected from the database of the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014. --- V617F --- --- V617F --- --- V617F --- --- V617F --- --- V617F ---

40 patients (14 male and 26 female) with JAK2 V617F positive ET without clinically apparent cardiovascular disease signed the informed consent and were enrolled in the study in 2014 - 2015 for the first examination and 36 (12 male and 24 female) of them are expected to participate also in 2018-19. --- V617F ---

3. JAK2 V617F/G1849T allele burden The ipsogen JAK2 MutaQuant Kit, Qiagen (ZDA) (Ref: No. 673523) will be used for the detection and quantification of JAK2 V617F/G1849T allele in genomic DNA extracted from peripheral blood of patients and also control subjects. --- V617F ---

3. JAK2 V617F/G1849T allele burden The ipsogen JAK2 MutaQuant Kit, Qiagen (ZDA) (Ref: No. 673523) will be used for the detection and quantification of JAK2 V617F/G1849T allele in genomic DNA extracted from peripheral blood of patients and also control subjects. --- V617F --- --- V617F ---

A SNP specific primer selectively amplifies the JAK2 V617F allele which is detected with a real-time qPCR instrument that quantifies the PCR products. --- V617F ---

The JAK2 V617F allele burden will be calculated and expressed as the percentage of JAK2 V617F mutated alleles throughout the whole JAK2 record. --- V617F ---

The JAK2 V617F allele burden will be calculated and expressed as the percentage of JAK2 V617F mutated alleles throughout the whole JAK2 record. --- V617F --- --- V617F ---

The association between the parameters of vascular function / morphology and the JAK2 V617F allele burden will be assessed by the Pearson correlation coefficient. --- V617F ---

Primary Outcomes

Description: Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid artery stiffness (expressed as two interrelated parameters, the beta-stiffness index and the pulse wave velocity) in a 4 year observation period?

Measure: Change of carotid artery stiffness (expressed by beta-stiffness index and pulse wave velocity) in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.

Time: the first visit in 2014-2015 and the second visit in 2018-2019

Description: Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of carotid plaque score in a 4 year observation period? Scoring of atherosclerotic plaques will be done according to the Rotterdam Study. The presence of at least one plaque in each segment of the extracranial carotid arterial bed, (the common carotid artery and the bulb, the internal carotid artery and the external carotid artery) on either side is scored 1 point. Thus, the carotid plaque score ranges from 0 (absence of plaques, best) to 6 (plaques present in all segments on both sides, worst outcome).

Measure: Change of carotid artery plaque score in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.

Time: the first visit in 2014-2015 and the second visit in 2018-2019

Description: Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show more advanced progression of coronary calcium score in a 4 year observation period?

Measure: Change of coronary calcium burden in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.

Time: the first visit in 2014-2015 and the second visit in 2018-2019

Description: Do patients with JAK2 V617F positive ET in comparison to age-and sex-matched, apparently healthy control subjects show greater changes digital endothelial function, expressed as the Reactive Hyperemia Index (RHI), in a 4 year observation period? The RHI is the ratio of the pletysmographic amplitude of the digital arteries during maximal reactive hyperemia and the basal amplitude. RHI ranges from 1 (no augmentation of pulsation with reactive hyperemia, i.e. worst outcome) to values above 2 (good endothelial response to reactive hyperemia).

Measure: Change of digital endothelial function, expressed as the Reactive Hyperemia Index, in JAK2 V617F positive ET patients in comparison to healthy control subjects in a 4-year period.

Time: the first visit in 2014-2015 and the second visit in 2018-2019

Description: Quantification of JAK2 V617F mutation burden and its correlation with the coronary calcium burden.

Measure: Association of the JAK2 V617F mutation burden with the coronary calcium burden.

Time: at inclusion in the years 2014-2015, and at the second visit in 2018-2019

41 A Pilot Study of Tazemetostat and MK-3475 (Pembrolizumab) in Advanced Urothelial Carcinoma

This phase I/II trial studies the side effects and best dose of tazemetostat and how well it works when given together with pembrolizumab in treating patients with urothelial carcinoma that has spread to nearby tissue or lymph nodes or other places in the body (locally advanced/metastatic). Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tazemetostat and pembrolizumab may work better in treating patients with urothelial carcinoma compared to pembrolizumab without tazemetostat.

NCT03854474 Advanced Urothelial Carcinoma Locally Advanced Urothelial Carcinoma Metastatic Bladder Urothelial Carcinoma Metastatic Urothelial Carcinoma Stage III Bladder Cancer AJCC v8 Stage IIIA Bladder Cancer AJCC v8 Stage IIIB Bladder Cancer AJCC v8 Stage IV Bladder Cancer AJCC v8 Stage IVA Bladder Cancer AJCC v8 Stage IVB Bladder Cancer AJCC v8 Biological: Pembrolizumab Drug: Tazemetostat
MeSH: Carcinoma Urinary Bladder Neoplasms Carcinoma, Transitional Cell
HPO: Bladder neoplasm Carcinoma

JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing are not eligible - Patients with a prior history of T-cell lymphoblastic lymphoma (T-LBL) or T-cell acute lymphoblastic leukemia (T-ALL) are not eligible - Patients who have received prior PD-L1/PD-1/PD-L2 or EZH2 inhibitor therapy are not eligible - Patients who have had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier are not eligible - Patients with a known additional malignancy that is progressing or requires active treatment are not eligible. --- V617F ---

Primary Outcomes

Description: Response rates will be summarized in each cohort by proportions and 95% exact confidence intervals. Time to progression will be summarized using the Kaplan-Meier product limit curve.

Measure: Objective response rate (ORR)

Time: Up to 1 year

Secondary Outcomes

Description: Will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5. All adverse events will be summarized as to type, grade, timing, frequency and attribution using frequencies and percentages

Measure: Incidence of adverse events

Time: Up to 30 days after treatment discontinuation

Other Outcomes

Description: Will determine if EZH2, H3K27me3 and mutations in genes associated with histone methylation determine disease response to EZH2 and PD1. Each gene will be related to response using Fisher's exact test.

Measure: EZH2 and H3K27me3 chromatin methylation and mutations in genes associated with histone methylation

Time: Baseline

42 Tazemetostat Expanded Access Program for Adults With Solid Tumors

Patients with following conditions are eligible to enroll in the EAP: - Epithelioid Sarcoma (ES) - Spindle cell sarcoma - Sinonasal carcinoma - Small Cell Carcinoma of the Ovary Hypercalcemic Type (SCCOHT) - Thoracic sarcoma - Poorly differentiated chordoma These conditions must be serious or life-threatening at the time of enrollment and appropriate, comparable, or satisfactory alternative treatments must have been tried without clinical success. Patients with conditions not listed above are not eligible for the tazemetostat EAP

NCT03874455 Epithelioid Sarcoma Spindle Cell Sarcoma Sinonasal Carcinoma Sm Small Cell Carcinoma of the Ovary Hypercalcemic Type Thoracic Sarcoma Poorly Differentiated Chordoma Drug: Tazemetostat
MeSH: Carcinoma Sarcoma Chordoma Carcinoma, Small Cell Small Cell Lung Carcinoma Carcinoma, Ovarian Epithelial
HPO: Carcinoma Chordoma Sarcoma Small cell lung carcinoma Soft tissue sarcoma

JAK2 V617F) observed in cytogenetic testing and DNA sequencing. --- V617F ---


43 PCM1-JAK2 Fusion Gene Detection in Patients With Therapy Related Myelodysplastic Syndrome / Acute Myeloid Leukemia Patients

The term "therapy-related" leukemia is descriptive and is based on a patient's history of exposure to cytotoxic agents. Although a causal relationship is implied, the mechanism remains to be proven. These neoplasms are thought to be the direct consequence of mutational events induced by the prior therapy Therapy-related myelodysplastic syndromes / acute myeloid leukemia (t- MDS / t-AML) is now considered a single entity, called therapy-related myeloid neoplasms based on the current World Health Organization WHO classification2,. It is a well-recognized clinical syndrome occurring as a late complication following Cytotoxic agents and ionizing radiotherapy in the treatment of most cancer types: Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), sarcoma, and ovarian and testicular cancerThe incidence of t-MDS/AML following conventional therapy ranges from 0.8% to 6.3% at 20 years. The median time to development of t-MDS/AML is 3 to 5 years, with the risk decreasing markedly after the first decade Two types of t-MDS/AML are recognized in the WHO classification depending on the causative therapeutic exposure: an alkylating agent/radiation-related type and a topoisomerase II inhibitor-related type. Alkylating agent-related t-MDS/AML usually appears 4 to 7 years after exposure to the mutagenic agent .The reciprocal translocation t(8;9) (p22;p24) between the short arm of chromosome 8 and the long arm of chromosome 9 is a recurrent abnormality that fuses the Janus activated kinase 2 (JAK2) to the human autoantigen pericentriolar material 1 gene (PCM1) , with breakage and reunion at bands 8p11 and 9q3410Due to PCM1-JAK2 gene fusion, the coiled-coil domains of PCM1 mediate an oligomerization that brings together the linked JAK2 domains resulting in a constitutively activated tyrosine kinase domain of JAK2The most common mechanism for JAK2 activation in hematologic malignancies is the point mutation at position 617 (V617F). The consequences of JAK2 activation are neoplastic transformation and abnormal cell proliferation in various malignancies - So, translocations involving the JAK2 locus are considered of oncogenic importance in acute leukemias and myelodysplastic/ myeloproliferative diseases. - Patients with this abnormality present with broad clinical spectrum ranging from chronic to acute hematological diseases with myeloid or lymphoid appearance

NCT03943394 Detection of PCM1-JAK2 Fusion Gene by FISH in the Two Types of t-MDS/AML and Relationship Between PCM1-JAK2 Fusion Gene and Cumulative Dose, Dose Intensity Other: fresh samples are obtained from patients for detction of PCM1- JAK2 fusion gene

Alkylating agent-related t-MDS/AML usually appears 4 to 7 years after exposure to the mutagenic agent .The reciprocal translocation t(8;9) (p22;p24) between the short arm of chromosome 8 and the long arm of chromosome 9 is a recurrent abnormality that fuses the Janus activated kinase 2 (JAK2) to the human autoantigen pericentriolar material 1 gene (PCM1) , with breakage and reunion at bands 8p11 and 9q3410Due to PCM1-JAK2 gene fusion, the coiled-coil domains of PCM1 mediate an oligomerization that brings together the linked JAK2 domains resulting in a constitutively activated tyrosine kinase domain of JAK2The most common mechanism for JAK2 activation in hematologic malignancies is the point mutation at position 617 (V617F). --- V617F ---

The most common mechanism for JAK2 activation in hematologic malignancies is the point mutation at position 617 (V617F). --- V617F ---

Primary Outcomes

Description: Using fresh sample from patients with myeloid neoplasm to search for PCM1-JAK2 fusion gene in the 2 types of thaerap related myeloid neoplasm , studying relationship between PCM1-JAK2 and dose intensity and time of exposure, and studying relationship between PCM1-JAK2 and other cytogenetic abnormalities by using FISH technique and

Measure: Detection of PCM1-JAK2fusion gene

Time: 24 months

44 Modulation of Morbidity and Disease Progression in Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Patients With Obstructive Sleep Apnea (OSA) by CPAP

This early phase I trial studies how well the use of a continuous positive airway pressure (CPAP) machine works in treating obstructive sleep apnea in patients with polycythemia vera or essential thrombocythemia. Obstructive sleep apnea is a condition where a person stops breathing during sleep, and is estimated to affect 30 to 50 percent of patients with polycythemia vera or essential thrombocythemia. A patient with obstructive sleep apnea typically snores, has disrupted sleep, experiences morning headaches, and has daytime sleepiness. Patients diagnosed with obstructive sleep apnea are typically treated with a device called CPAP. The CPAP provides pressurized air that keeps upper air passages open during sleep and may prevent them from narrowing or collapsing as occurs during snoring or sleep apnea.

NCT03972943 CALR Gene Mutation Essential Thrombocythe Essential Thrombocythemia JAK2 Gene Mutation MPL Gene Mutation Obstructive Sleep Apnea Syndrome Polycythemia Vera Procedure: Continuous Positive Airway Pressure Other: Patient Observation Other: Questionnaire Administration
MeSH: Polycythemia Vera Apnea Sleep Apnea Syndromes Sleep Apnea, Obstructive Polycythemia Thrombocytosis Thrombocythemia, Essential
HPO: Apnea Obstructive sleep apnea Polycythemia Sleep apnea Thrombocytosis

Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.. Change in JAK2 V617F allele burden. --- V617F ---

Primary Outcomes

Description: Will be tested at the two-sided 0.025 significance level to provide overall control of the type I error for the co-primary endpoints at 0.05. The endpoints will be summarized by mean, median, range, standard deviation, interquartile range and boxplots. Scatterplots will be used to show bivariate associations. An assessment of normality will be made prior to statistical testing. Paired t tests will be used to analyze endpoints that are sufficiently Gaussian in distribution. Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.

Measure: Change in Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)

Time: Baseline, after 3 months, and after 6 months on trial

Description: Will be tested at the two-sided 0.025 significance level to provide overall control of the type I error for the co-primary endpoints at 0.05. The endpoints will be summarized by mean, median, range, standard deviation, interquartile range and boxplots. Scatterplots will be used to show bivariate associations. An assessment of normality will be made prior to statistical testing. Paired t tests will be used to analyze endpoints that are sufficiently Gaussian in distribution. Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.

Measure: Change in JAK2 V617F allele burden

Time: Baseline, after 3 months, and after 6 months on trial

Other Outcomes

Description: Assessed by Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference and Gender (STOP-BANG) questionnaire. The proportion of patients whose results indicate a diagnosis of OSA will be calculated. All patients with a diagnosis of OSA, regardless of whether they are enrolled to the treatment component of the study, will be counted towards the assessment of prevalence. An assessment of normality will be made prior to statistical testing. Paired t tests will be used to analyze endpoints that are sufficiently Gaussian in distribution. Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.

Measure: Proportion of patients with a diagnosis of obstructive sleep apnea (OSA)

Time: During the OSA screening

Description: The endpoints will be summarized by mean, median, range, standard deviation, interquartile range and boxplots. Scatterplots will be used to show bivariate associations. An assessment of normality will be made prior to statistical testing. Paired t tests will be used to analyze endpoints that are sufficiently Gaussian in distribution. Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.

Measure: Leucocytes, platelets, red cell counts, and tumor necrosis factor (TNF) analysis

Time: Baseline, after 3 months, and after 6 months on trial

Description: Will be measured in blood samples taken from all patients. OSA-related adverse events reported in the Treatment Cohort at these timepoints will be correlated with these marker levels. Pearson or Spearman correlation will be used to assess correlation between thrombo-inflammatory markers and oximetric abnormalities.

Measure: Thrombotic and inflammatory marker levels for all patients

Time: Baseline, after 3 months, and after 6 months on trial

45 A Phase III, Randomised, Open-label, Multicenter International Trial Comparing Ruxolitinib With Either HydRoxycarbamIDe or Interferon Alpha as First Line ThErapy for High Risk Polycythemia Vera

The trial will be a phase III, randomised-controlled, multi-centre, international, open-label trial consisting of ruxolitinib versus best available therapy, where best available therapy is a choice of interferon alpha, any formulation permitted (IFN) or hydroxycarbamide (HC), and which will be elected by the Investigator prior to randomisation.

NCT04116502 Polycythemia Vera Drug: Ruxolitinib Drug: Hydroxycarbamide Drug: Interferon-Alpha
MeSH: Polycythemia Vera Polycythemia
HPO: Polycythemia

Peripheral blood JAK2 V617F allele burden. --- V617F ---

Symptom burden/(QALY)quality of life years gained 7. Health economics including cost utility and cost effectiveness analyses 8. Peripheral blood JAK2 V617F allele burden according to ELN response criteria 9. Rates of discontinuation 10. --- V617F ---

Primary Outcomes

Description: Event Free Survival

Measure: Event Free Survival (EFS)

Time: the time from randomisation to the date of the first major thrombosis/haemorrhage, death,transformation to Myelodisplastic Syndromes, Acute Myeloid Leukaemia or Post-polycythemia Vera Myelofibrosis, if within the ~3 year trial period

Secondary Outcomes

Description: As defined in the protocol, combined and split to venous and arterial

Measure: Major thrombosis

Time: Occuring while on treatment (over 3 years)

Description: As defined in the protocol

Measure: Major haemorrhage

Time: Occuring while on treatment (over 3 years)

Description: Transformation to PPV-MF

Measure: Transformation to PPV-MF

Time: Occuring while on treatment (over 3 years)

Description: Transformation to MDS and/or AML

Measure: Transformation to MDS and/or AML

Time: Occuring while on treatment (over 3 years)

Description: As defined by ELN response criteria at 1 year

Measure: Complete Haematological remission (CHR)

Time: 1 year post-treatment

Description: As measured via MPN-SAF

Measure: Symptom burden/Quality of life (MPN-SAF)

Time: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

Description: As measured via MDASI

Measure: Symptom burden/Quality of life (MDASI)

Time: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

Description: As measured via EQ-5D

Measure: Symptom burden/Quality of life (EQ-5D)

Time: Questionnaires collected at baseline, weeks 12, 26, 39, 55, months 15, 18, 24, 30 and 36

Description: Including cost utility and cost effectiveness analyses as defined by the protocol (e.g. QALYs)

Measure: Health economics

Time: At the end of the trial (trial duration of approximately 8 years)

Description: According to ELN response criteria

Measure: Peripheral blood JAK2 V617F allele burden

Time: At baseline and annually throughout the trial (from baseline until approximately 3 years post-randomisation)

Description: Trial discontinuation

Measure: Rates of discontinuation

Time: From treatment prior to protocol defined 3 years

Description: collected according to CTCAE version 4.0 and the MITHRIDATE protocol

Measure: Rate and severity of adverse events

Time: Continuous throughout the trial (from randomisation until approximately 3 years post-randomisation))

Description: in patients with splenomegaly

Measure: Spleen response

Time: Response at 1 year post randomisation

Description: Time free from venesection

Measure: Time free from venesection

Time: Defined as the mean time between venesections while on trial treatment (treatment duration of 3 years)

Description: Malignancy independent to the original diagnosis

Measure: Secondary malignancy

Time: Occuring throughout the trial (from randomisation until approximately 3 years post-randomisation)

Description: Change in QRisk score

Measure: Change in QRisk score

Time: Collected at baseline and years 1, 2 and 3

Other Outcomes

Description: Progression of marrow fibrosis (bone marrow collected and analysed at the Weatherall Institute of Molecular Medicine (WIMM) in Oxford

Measure: Progression of marrow fibrosis

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: Impact of treatment on molecular signatures of disease (as analysed by the WIMM in Oxford)

Measure: Impact of treatment on molecular signatures of disease

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: within the stem/progenitor cell compartment (as analysed by the WIMM in Oxford)

Measure: Clonal involvement

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: (acquisition of additional mutations, as analysed by the WIMM in Oxford)

Measure: Clonal evolution

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: of other disease-association mutations (as analysed by the WIMM in Oxford)

Measure: Reduction of peripheral blood allele burden

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: and any change over time (as analysed by the WIMM in Oxford)

Measure: Assessment of the prevalence of clonality markers for haematological disease

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: (angina, acute coronary syndrome, acute MI; arrhythmia)

Measure: Cardiac event

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: Pulmonary hypertension as assessed clinically

Measure: Pulmonary hypertension

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: e.g. angiogram, angioplasty, CABG

Measure: Coronary intervention

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: e.g. LVEF% on ECHO/MUGA and/or NYHA classification

Measure: Deterioration in cardiac function

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: TIA, haemorrhagic CVA, non-haemorrhagic CVA

Measure: Cerebrovascular event

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: peripheral vascular disease: claudication, carotid stenosis

Measure: Arterial vascular event

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: including DVT, PE, Cerebral, splanchnic, other

Measure: Venous thrombosis

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

Description: Pregnancy loss

Measure: Pregnancy loss

Time: Occuring throughout the trial (from randomisation to approximately 3 years post-randomisation)

46 Tazemetostat Expanded Access Program for Adults With Epithelioid Sarcoma

A multicenter, open-label expanded access program to provide access to tazemetostat to Epithelioid Sarcoma (ES) patients in serious need who are otherwise unable to participate in a clinical study or whom access is not available through marketed product in the US.

NCT04225429 Epithelioid Sarcoma Drug: Tazemetostat
MeSH: Sarcoma
HPO: Sarcoma Soft tissue sarcoma

JAK2 V617F) observed in cytogenetic testing and DNA sequencing. --- V617F ---


47 A Prospective, Single-center Clinical Trial of Pegylated Interferon Alfa-2b Versus Interferon Alfa Therapy in the Treatment of Childhood Essential Thrombocythemia

Objectives: To compare the efficacy and safety in children (<18 years) diagnosed as essential thrombocythemia treated with the Pegylated Interferon Alfa-2b vs. Interferon Alfa. Study Design: A prospective, open-label, nonrandomized, single-center clinical trial

NCT04226950 Essential Thrombocytopenia Drug: Recombinant Interferon Alpha Drug: Pegylated interferon alfa-2b
MeSH: Thrombocytopenia Thrombocytosis Thrombocythemia, Essential
HPO: Thrombocytopenia Thrombocytosis

- Platelet count ≥ 450 × 109 / L for more than 6 months(If the patient has JAK2 V617F, CALR or MPL gene mutation, the history may be less than 6 months) - Platelet count ≥ 1000 × 109 / L at screening - The guardians has provided written informed consent prior to enrollment Exclusion Criteria: - Known to meet the criteria for primary myelofibrosis or polycythemia vera by 2016 WHO criteria - Presence of any life-threatening co-morbidity - Secondary thrombocytosis - Familial thrombocytosis - Resistance, or intolerance, or any contraindications to interferon - Interferon is used in the past 1 month before enrollment - Patients with previous or present thrombosis or active bleeding - WBC<4× 109 / L - HGB<110g/L - Poor control of thyroid dysfunction - Patients with a prior malignancy within the last 3 years - Patients with severe cardiac or pulmonary dysfunction - Severe renal damage (creatinine clearance < 30 ml / min) - Severe liver dysfunction (ALT or AST > 2.5×ULN) - Patients diagnosed as diabetes with poor control - Patients with hepatitis B virus, hepatitis C virus replication or HIV infection - Patients with a history of drug / alcohol abuse (within 2 years before the study) - Patients that have participated in other experimental researches within one month before enrollment - History of psychiatric disorder - Any other circumstances that the investigator considers that the patient is not suitable to participate in the trial Inclusion Criteria: - <18 years old - Male or Female - Diagnosis of essential thrombocythemia according to the 2016 WHO criteria. --- V617F ---

- Platelet count ≥ 450 × 109 / L for more than 6 months(If the patient has JAK2 V617F, CALR or MPL gene mutation, the history may be less than 6 months) - Platelet count ≥ 1000 × 109 / L at screening - The guardians has provided written informed consent prior to enrollment Exclusion Criteria: - Known to meet the criteria for primary myelofibrosis or polycythemia vera by 2016 WHO criteria - Presence of any life-threatening co-morbidity - Secondary thrombocytosis - Familial thrombocytosis - Resistance, or intolerance, or any contraindications to interferon - Interferon is used in the past 1 month before enrollment - Patients with previous or present thrombosis or active bleeding - WBC<4× 109 / L - HGB<110g/L - Poor control of thyroid dysfunction - Patients with a prior malignancy within the last 3 years - Patients with severe cardiac or pulmonary dysfunction - Severe renal damage (creatinine clearance < 30 ml / min) - Severe liver dysfunction (ALT or AST > 2.5×ULN) - Patients diagnosed as diabetes with poor control - Patients with hepatitis B virus, hepatitis C virus replication or HIV infection - Patients with a history of drug / alcohol abuse (within 2 years before the study) - Patients that have participated in other experimental researches within one month before enrollment - History of psychiatric disorder - Any other circumstances that the investigator considers that the patient is not suitable to participate in the trial Essential Thrombocytopenia Thrombocytopenia Thrombocytosis Thrombocythemia, Essential This is a prospective, open-label, nonrandomized, single-center clinical trial between Interferon Alfa and Pegylated Interferon Alfa-2b in childhood essential thrombocythemia (<18 years). --- V617F ---

Primary Outcomes

Description: Proportion of subjects with a platelet count <600×109/L after 3 months of treatment will be evaluated.

Measure: Change in platelet count

Time: 3 months

Secondary Outcomes

Description: To compare the complete hematologic response rates between different treatment groups

Measure: The complete hematologic response rates

Time: 3 months

Description: Time to response in platelet count (<600×109/L) between different treatment groups

Measure: Time to response in platelet count

Time: 3 months

Description: To compare the proportion of subjects that display change on key biomarkers of the disease- JAK2V617F, CALR, MPL mutations.

Measure: Impact of therapy on key biomarkers

Time: 12 months

Description: To estimate incidence of major cardiovascular and thrombotic events (defined as cardiovascular death, myocardial infarction, stroke, transient ischemic attack, pulmonary embolism, Budd Chiari syndrome, deep vein thrombosis, and any other clinically relevant thrombotic event) while on active treatment or observation following end of treatment between different treatment groups

Measure: Incidence of major cardiovascular and thrombotic events

Time: 12 months

Description: To estimate incidence of development of myelodysplastic disorders, myelofibrosis, or leukemic transformation between different treatment groups

Measure: Incidence of development of myelodysplastic disorders, myelofibrosis, or leukemic transformation.

Time: 12 months

Description: To compare the proportion of subjects that display change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (0-100 scores, higher scores mean a worse outcome) between different treatment groups.

Measure: Change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom score

Time: 3 months

Description: To compare incidence of specific pre-defined toxicity including fatigue, flu-like symptoms, dizziness, injection site necrosis, dyspnea, pain, depression, blurred Vision, insomnia, anorexia, weight Loss, weakness, pruritis, sweating, fever, decreased Libido, hot Flashes, flushing.

Measure: Specific pre-defined toxicity

Time: 12 months

Description: To compare the proportion of subjects that display change on bone marrow histopathology

Measure: Impact of therapy on bone marrow histopathology

Time: 12 months

Description: To compare the proportion of subjects that display change on cytogenetic abnormalities.

Measure: Impact of therapy on cytogenetic abnormalities

Time: 12 months

Description: To compare the incidence of death while on active treatment or observation following end of treatment

Measure: Death while on active treatment or observation following end of treatment

Time: 12 months


HPO Nodes


Polycythemia
Genes 19
EPO CCND1 ACVRL1 GATA1 VHL EPAS1 EGLN1 FH SLC30A10 SLC30A10 CYB5R3 SH2B3 PKLR JAK2 JAK2 EPOR BPGM ENG VHL
Thrombocytosis
Genes 37
TTC37 RPSA MPL THPO HMGCL SKIV2L CD55 ACAT1 TBC1D24 THPO CALR SH2B3 PMM2 TTC37 MTHFD1 ADA2 JAK2 RUNX1 TET2 LMNA JAK2 JAK2 CALR IFNGR1 ELANE MPL RPS14 SF3B1 RPS19 HBB STING1 MPL BCR TET2 JAK2 ABL1 ZMPSTE24
Neoplasm
Genes 1473
GPC3 LETM1 LZTS1 REST MPL ARID1B RPL18 MGMT GLI3 BIRC3 ZSWIM6 TRNS2 ETV6 HNF1B KIT BRCA1 SUFU PLAG1 SOX9 TP63 CTSC RASA1 ATRX TRIM37 SUFU BTK CYP11B1 NOTCH3 EPCAM PORCN PIGL AR TET2 FH TGIF1 HMBS ATRX TREX1 SMAD4 KRT17 FGFR1 WDPCP SF3B1 GPR101 KIT GLI1 SLC25A11 XRCC4 SDHD PRKCD RNF43 SDHB BAP1 EGFR PIGA NF1 ASCL1 MPL RET C2CD3 GDNF NR5A1 DICER1 TNFRSF4 CASP10 TERC FGF8 PSAP CIB1 SLC22A18 PTCH2 ENPP1 CDKN2C SLC25A11 GPR101 KIT AXIN2 TREX1 DYNC2LI1 ERCC4 RPS14 COMP TINF2 FOXE1 DHCR24 RPS7 TYROBP HOXD13 ERBB2 BLK EYA1 ZFPM2 ERCC6 NLRP1 STAC3 ERCC5 NUTM1 MEN1 WT1 BCL10 GNPTAB KRAS TP53 KDR PUF60 TRNF FCN3 SDHC KCNH1 MSTO1 EP300 BUB1B GNA11 KCNE3 DOCK8 SEMA3C ACD GLI2 SMPD1 SUFU NF1 PTCH2 ACAN DCC WT1 CTSA KIF11 BCR SRGAP1 KIT PTEN LEMD3 MLLT10 SCN4A BRCA2 BMPR1A NOTCH3 SEC23A CDKN1C BARD1 SPIB RSPO1 MC2R CALR ATP6V1B2 NBN RAD54L MST1 SUFU MYCN TMEM127 SRD5A3 IGF2 CD28 RUNX1 OGG1 HAX1 SDHC CTNNB1 MST1R SDHA IGF2 KCNJ10 IL12RB1 MEN1 RAD51 TFE3 ND5 MMEL1 MVK APC FLI1 RNF6 NF1 BRCA2 SUFU GPC6 NR4A3 TTC37 KIT NRTN BLNK IGH SPRED1 TXNRD2 IGF2R FOXP1 BUB1B SOS1 LRP5 GJB2 DNMT3A PMS2 PRKN RET MSH6 ACVRL1 MPLKIP ERCC2 AIP GNAS TAL1 NNT RECQL4 PMS1 DLL1 EIF2AK4 STAT6 MNX1 SDHB KRAS MEN1 MN1 SH2B3 EFL1 VHL KLLN RMRP RUNX1 SIX3 GDNF FANCD2 EXT1 CDH23 BRD4 DLEC1 NODAL CARMIL2 SDHB MSH2 HMBS SMAD4 SRP72 NRAS DOCK8 SPRTN BRCA1 MAP2K1 KRT14 LETM1 TERT MAP2K2 HRAS WHCR WT1 IDH1 TMEM107 SCN10A GJB3 SDHD KRAS GATA1 RPS20 GJB2 SLX4 USP8 PRKAR1A CR2 JAK2 HFE MPL POT1 BRCA2 GNAI3 SDHB ALK OCA2 TP53 GPC4 ACTG2 CTNNB1 HSPG2 AR FGFR1 STK4 MET TMC8 MRAP MSH6 CCBE1 EWSR1 LMO1 EDN3 LEMD3 PGM3 FGFR3 CASP8 RB1CC1 SCN9A FANCL TG SDHD COX3 IGF2 COL11A2 AGGF1 GPR101 PRKN PLCB4 SDHD NF1 GTF2E2 MAP2K1 ESCO2 CDC73 WRAP53 TET2 PDGFRB RNASEH2A RAD21 HNF1A TGFBR2 POLD1 COX2 TNFRSF10B MINPP1 DNAJC21 FAS EXT1 SLC26A2 APC SDHAF2 TINF2 LIG4 POLR1D WWOX TMC6 RPS19 ERCC2 SASH1 MC1R MVD SEC23B CYP2A6 GPC3 KIT HRAS RAD54L SDHA GDNF NKX2-1 GFI1 ALX3 STAT3 MYH11 DYNC2LI1 FGFR2 TCOF1 PTEN MAFA PIK3R1 SLC25A13 HRAS VHL COL7A1 GNAS FGFR2 PIK3CA GPC4 DICER1 ERCC3 PIK3CA RAD51C RB1 RMRP MLH3 ATM COL7A1 LIG4 NF1 VAMP7 RPL35A RB1 SETD2 BCL10 LPP NRAS KRAS ABCA5 ERCC2 PDE6D KCNQ1OT1 MS4A1 SLC22A18 APC LIG4 JAK2 FANCD2 GAS1 STAG3 NRAS PALLD SLC22A18 RFWD3 PPP2R1B APC PTPN11 PTEN WIPF1 PIK3CA NOP10 IL7 UROD TNFRSF1B TP53 REST SLC37A4 NHP2 CXCR4 KIT CYSLTR2 FZD2 ALX4 BMPR1A SRY TRNQ SDHD PIGL CCM2 FIBP FANCI GJB4 SPINK1 RPL10 NSD2 MAP3K1 RET CDK4 HSPA9 TET2 GFI1B MAD2L2 DCC AP2S1 SMAD7 BRCA2 TRNK ERCC3 BRCA1 ELANE SFTPC PTH1R COL1A1 FUZ OFD1 RET FLT4 PRKAR1A SBDS RPL26 SMARCE1 SMARCAD1 MSH2 BCR GPR35 INTU FANCA STAT1 ANTXR2 FGFRL1 TUBB BRAF SLX4 CASP10 TERT RAD21 MTOR TRIP13 MYD88 DPM1 RSPO1 PTPN11 CTNNB1 AIP PTEN VANGL1 CYP2D6 RPS10 GCK KRT16 DNAJC21 BCL2 AKT1 KRAS KLF6 NOTCH1 FLNA MAX NF2 PALB2 TP53 PSENEN RNF6 TSC1 HNF1B TP53 RFWD3 SDHD PERP TP53 DIS3L2 B3GALT6 STS PDGFB SMARCB1 BRAF BRIP1 CBFB BUB1 BLM INHBA CALR NBN MLH3 TAF1 MLF1 PIK3CA MSH2 CTLA4 ND6 PALB2 WT1 PTCH1 POLE ADA MC1R FLT4 ATP7A MLH3 SMO TRNF NRAS LMNA DLST TRNL1 MTAP TP53 ZAP70 SDHB CHEK2 PALB2 FLT4 CDK4 NBN MSR1 CC2D2A TNPO3 ECE1 RPS15A NAGS TMEM67 HNF1A PIK3CA ATP7A AKT1 NRAS SDHAF2 CXCR4 TSC2 NF2 EPHB2 WDPCP OFD1 BUB1 FLT3 APC SMARCA4 CDKN2A RPS29 MCM4 PDGFRA ESCO2 CTC1 ESR1 SDHB MSH6 APC HABP2 GNAQ KIF1B SH3GL1 CD70 MPL IGH ZIC2 GCM2 VEGFC HRAS CTNNB1 KCNH1 LRRC8A BRAF FAS ICOS NSD1 RNF43 AKT1 BIN1 DLC1 SH2B3 RARA WNT10A CARD14 SDHC EXOC6B ESCO2 POLR1C G6PC MSH6 KRT1 PDX1 TNFRSF13C ERCC3 EVC SNAI2 CD79A BRCA1 RNASEH2B CCND1 TP53 RPS19 H19 H19 BRCA2 TFAP2A ARMC5 FASLG FGFR3 APC F5 EDN1 MAP3K8 AIP APC AKT1 TERC CCND1 CEL MYC TP53 GPC4 ERCC5 HNF1A POLE DAXX NUP214 TRIP13 AKT1 TET2 CDC73 ND1 MUTYH PIK3R1 TERT CEBPA EXT2 OCRL DIS3L2 ADAR TGFBR2 BRCA2 MRE11 SOS1 HNF4A FAH TMEM127 WT1 AXIN2 TCF4 EDN3 PTPN3 KRAS SEMA4A PIK3CA XPA MFN2 TINF2 PIK3CA APPL1 RUNX1 GNPTAB FGFR3 NRAS PDCD10 RAG2 PTEN CTNNB1 SOX2 BMPR1A HBB TERT USP9X NFKB1 FANCC PRF1 WRN SRY SRSF2 PMS2 RHBDF2 PHOX2B RPS17 PAX3 RECQL4 KIF1B SQSTM1 RB1 EXT1 XPC CYLD TOP2A MYD88 CDKN1B TET2 GJB2 PTEN UBE2T RTEL1 PTCH1 KLHDC8B GATA1 POLH JAK2 RHOH FLCN DCLRE1C MTMR14 GTF2H5 PTEN SBDS TBC1D24 PAX7 AR TP53 ASPSCR1 MTM1 RECQL4 ERCC2 TGFBR2 ERCC4 JAK2 SF3B1 CDKN2B XPC GATA4 KIT POU2AF1 BRCA2 GREM1 CDON NTHL1 DICER1 GINS1 ATM RAD51D SHOX EXT1 RASGRP1 WT1 GATA2 NF2 ERCC4 TUBB MBTPS2 DHCR7 MYLK KCNN3 TCTN3 TMEM216 TMEM231 KRT1 CTNNB1 MPL PDGFRB FANCG RPGRIP1L KEAP1 DICER1 WT1 BAP1 FOXI1 ERCC4 CDKN2A FGFR3 KDSR CBL HRAS BMPR1A DISP1 RELA MAP3K1 PARN BCR ENG COL7A1 LMOD1 KRAS PAX6 SNAI2 GLI3 FANCF FOXO1 RPL15 TBX18 TRPV3 PIK3CA NRAS CDH1 GNAS SMARCB1 KLF11 ADA2 EDN3 POU6F2 CDH1 GNAS IL1B SMAD4 H19-ICR SDHB STK11 NF2 TRIM28 SEC23A SLCO2A1 BRCA2 BRAF DNMT3A MDM2 BMP2 BRCA2 DHH NRAS POU6F2 CTBP1 PTCH2 FLCN CALR BAP1 LIG4 HRAS REST BRAF SAMD9 NDP TYR KRT17 MUC5B PRSS1 MEN1 NPM1 ITK MSH2 CYLD TAL2 SRP54 IFIH1 HMMR TCTN3 ND5 JAK2 FAM20C RET NEK9 DMRT3 KRAS MINPP1 SH3KBP1 THPO FAH KRT5 JAK2 PHKG2 TSC1 TNFRSF13C MEN1 FH RPL31 FANCG PIK3CA IL2RG DNAJC21 VANGL2 MYO1H ALX1 CDKN2A AIP H19 NRAS TWIST1 PTEN TRNK TRPS1 RPS26 MAPRE2 RPS27 TCF3 KRT17 ERCC6 DHH MMP1 FGFR1 SEMA3D PTCH1 ABL1 CDKN2A SKI APC WWOX ZSWIM6 NF2 WNT10A KRAS GPC3 REST GJB6 HRAS VHL CTNNB1 TGFBR1 IL6 TDGF1 RPL11 IL1RN BRCA1 MGAT2 POT1 ASCC1 XPA TBX2 FLCN HFE NTHL1 SMARCB1 DVL3 TRNH IDH1 FANCA LAMB3 CD79B RAD51C PRDM16 PHOX2B GNAQ CCL2 PDGFRA CREB1 SRP54 PIEZO2 TRNL1 GBA GNAS WNT5A PIK3CA STS FANCB KRAS MAGT1 RAD51 IDH1 TNFRSF13B TREM2 GABRD BCL10 SKIV2L POLD1 KRIT1 KRAS ARSA SMAD4 RAD51 TP53 DIS3L2 KIAA0753 PRLR CD96 LZTR1 WRN GATA2 EDNRB MUTYH ATM CHIC2 TP53 CYLD PAX4 SLC26A4 RTEL1 VHL NEK1 TRNS1 GCM2 TYR ATP7B CTHRC1 BRAF ASXL1 OFD1 MLH1 CDKN1A PHOX2B XRCC2 CD19 RB1 FOXC2 TRIM28 EWSR1 TERT GNA11 F13B CDKN2A KARS1 BCL10 TP53 WT1 CDKN2A FDPS KIT COX1 COL14A1 VHL WT1 TERT SMAD4 STAR NUMA1 RPL5 PDGFB PCGF2 CFTR KCNQ1OT1 KIT GJA1 GNAQ CD27 FANCC IDH2 EVC2 BRCA2 TCF4 KRAS PIK3CA CDC73 ACVR1 BRIP1 TRNW PRCC GCGR CDKN1B STK11 SCN11A TGFBR2 AXIN2 ERBB2 RPL35 APC TSC2 IL12A SSX2 TET2 KIF1B DICER1 TRNP BTK CCDC22 PDGFRA ALX3 ADAMTS3 CD81 RET DKC1 GLI3 FGF3 SMAD4 STK11 ERCC6 WT1 ELANE C11ORF95 SAMD9L SLC45A2 NQO2 PTPN11 ATR PDGFRL TNFSF12 BRCA2 ADA BUB1B FASLG GDF5 KRAS CPLANE1 CREBBP CDC73 CLCNKB GATA2 CTRC SDHA ACTB APC BMPER SPINK1 APC2 MC1R FOXI1 DYNC2H1 KIT PPM1D SDHC NSD1 SDHC DDX41 ANTXR1 CASP8 F13A1 SUFU INS NUP214 ANTXR2 KIF7 NFKB2 ABCC8 TARS1 ERCC3 TCIRG1 ND4 ERCC2 GNAS TERT WASHC5 SLC49A4 RERE CALR MSH3 PHOX2B SLC25A13 BMPR1B CYLD SIX6 ASCL1 IDH2 FAN1 CHRNG CBL NEUROD1 MSH3 THPO VANGL1 CDKN2B TAF15 PTCH2 HMGA2 MSH6 CHEK2 FN1 GATA2 IRF1 KRAS BMPR1A NPM1 ERCC3 CDH1 ALK DNM2 ERBB3 PTPN11 DLST MUTYH PARN GFI1 NBN FGFR3 CHEK2 EP300 RNF113A TNFSF15 TEK TERF2IP ICOS COL18A1 TNFSF12 BRAF CHEK2 IFNG TMC6 USB1 KDM6B GJC2 SLC26A2 MDH2 TP53 ENG MLH1 KRT6B MNX1 PDGFB TRNH POLE CASP10 HPGD TET2 RB1 PHOX2B JAG1 GNB1 ACD TNFRSF13B MYC BRAF TSC1 SAMD9L BCL10 H19 POT1 USP8 IGF2 OFD1 CYP11B2 KCNQ1 CDH1 LMX1B TET2 ANTXR1 JAK2 SMARCB1 ELMO2 PTCH1 SIX1 L2HGDH WRAP53 BUB3 AXIN1 RET KCNJ11 ABL1 FANCE RAD54B FANCM TSC2 MAX IGHM TSC1 HACE1 CASR RNF139 MITF RAF1 WT1 TCTN3 POLH LIG4 TP53 KRT10 AAGAB SRY RAD50 TNFRSF1B TRNQ DNASE1L3 FAM149B1 KRT9 VHL FLCN TBXT SLC37A4 DKC1 PNP DDB2 SETBP1 ECM1 MSH2 CR2 COL2A1 COL7A1 MLH1 FH SFTPA2 PIK3CA FOXH1 MET HNF4A H19 KAT6B GPR143 PHB PMS1 ATP7A FAT4 TJP2 TFAP2A GDF2 AHCY TSC2 CD19 TRNS1 BDNF TRIP13 AKT1 FGFR2 RAG1 BRCA1 SDHC MLH1 XRCC3 NSD2 LMNA SDHC TERC EXT2 PIK3CA MSH3 SDHD SRC CHEK2 C1S ABCA5 HBB RYR1 FGFR2 CDC73 KIT FANCE RET LYST KCNJ10 BCHE HDAC4 INPP5E CRKL PHOX2B BAP1 CPLX1 PDGFRB ARL6IP6 RNASEL SETBP1 CTLA4 PALB2 DCLRE1C NSUN2 XIAP TRNS2 BMPR1A IL7R BCL6 COL4A5 PIK3CA NOD2 PRKAR1A NELFA IL2RG MYH8 RHBDF2 IGLL1 PIK3CA SERPINA1 FOXE1 ARHGAP26 TCF4 MITF ABCB11 ERBB2 GNA14 SLC26A2 NSD1 SH2B3 STK11 PTCH1 GDNF RPL27 DHCR7 WAS CIB1 SHH CACNA1S LIN28B SF3B1 ATM PRKCD RPS24 LAMA3 ATRX CASP8 AKT1 OPCML HFE SH2D1A ING1 CCND1 SLC12A3 HABP2 H19 LAMC2 RAD51C NAB2 NRAS MAPK1 CPLANE1 CYP26C1 CDKN1B CHD7 IGH MYF6 BLM ASXL1 FH NEK1 HLA-DRB1 SLC26A4 RPS14 SHOX RNASEH2C SMARCD2 GATA2 CDH23 WT1 EPCAM NR0B1 KLLN DVL1 SEC23B GPC3 SLC17A9 BRCA1 SRP54 DKC1 RECQL4 CD28 PTPN11 HRAS NBEAL2 BARD1 MLH1 DDB2 PMS2 IRF1 ABCC6 EXT2 ASXL1 TSR2 PTEN MALT1 PTEN BCR PALB2 BRIP1 SSX1 PHKA2 FGFR2 SDHB FERMT1 KCNAB2 FLT3 PMVK MSTO1 CEP57 MMP1 PICALM IRF5 TP53 PTPRJ RNR1 WWOX PLCD1 RPS28 FGFR3 COL2A1 IKBKG TERT RASA1 SAMHD1 PHF21A
Myeloproliferative disorder
Genes 14
CALR THPO PDGFRA CALR SH2B3 JAK2 GATA2 BCR ABL1 PDGFRB MPL SH2B3 GATA1 RUNX1
Sarcoma
Genes 197
REST RB1 SDHC KRAS PAX7 ABCA5 ASPSCR1 RECQL4 SUFU APC ANTXR2 FH GREM1 KRT17 EXT1 PIK3CA BMPR1B RASGRP1 KIT SDHD PRKCD REST KCNN3 IDH2 NF1 CTNNB1 PDGFRB CDKN2B KEAP1 DICER1 DICER1 TAF15 CDKN2A FGFR3 SLC22A18 PTCH2 CDKN2C NBN CHEK2 EP300 AXIN2 CHEK2 IFNG PTH1R COL1A1 FOXO1 TBX18 GJC2 FLT4 PRKAR1A DHCR24 MSH2 MLH1 ANTXR2 GNAS CASP10 TRIP13 NUTM1 MDM2 TSC1 PTEN KCNH1 BUB1B FLNA NF2 ELMO2 NF1 BUB3 DCC MEN1 TSC1 MSH2 TP53 PTEN FAM20C PDGFB BUB1 NOTCH3 ATP6V1B2 TSC1 SUFU FLCN WT1 MSH2 MEN1 FH NRAS MTAP APC NF1 CHEK2 NR4A3 NBN APC NF2 TSC2 IL6 SPRED1 AKT1 NRAS BUB1B SOS1 FLCN SDHC SMARCB1 IDH1 LMNA MSH6 SDHC TSC2 NF2 SRC BUB1 APC RECQL4 ABCA5 SDHB GNAS APC PDGFRB VEGFC HRAS KCNH1 FAS BRD4 PRLR DLC1 SDHB PIK3CA WRN TP53 MAP2K1 IDH1 BRAF MLH1 CDKN1A RPS19 FOXC2 EWSR1 PTCH1 APC AKT1 CDKN2A KIT TP53 PDGFB AKT1 MSH6 EWSR1 CDC73 KIT NRAS IDH2 EXT2 CDKN1B SOS1 NF1 KLLN APC TSC2 SSX2 SEC23B DICER1 PIK3CA PDGFRA FAS EXT1 APC RECQL4 HRAS MLH1 CTNNB1 BMPR1A PMS2 EXT2 WRN PTEN SSX1 SDHA PTPN11 SDHB BUB1B PAX3 FASLG GDF5 CEP57 SQSTM1 CDC73 EXT1 TP53 PTPRJ CDKN1B PLCD1 RB1 APC PTCH1 MC1R
Carcinoma
Genes 16
POLE MSH2 DKC1 SMARCA4 NLRP1 POLD1 CDKN1B MLH1 RSPO1 FGFR3 BCL10 APC STK11 PTEN APC KIT
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Pulmonary arterial hypertension
Genes 126
LIFR GDF2 CAV1 TNFSF11 ABCD4 GJA1 PAM16 ARHGAP31 SPECC1L TRNH AGPAT2 CHST3 MED12 ACVRL1 BMPR2 FOS ND4 FGFR3 HBB FGFR1 EIF2AK4 TRNL1 GBA ACTA2 CCR6 CAV1 NOTCH1 COLQ PIGA DOCK6 TRNQ MPL SLC25A24 COG1 SFTPB SMAD4 LAMA2 SMAD9 TRNS2 CAV1 LIPA NOD2 SNX10 IRF5 KRAS CAV1 BSCL2 ALMS1 FLNA KRT18 GBA TRNS1 LIPT1 BMPR2 BANF1 SFTPC FIG4 KCNK3 FOXF1 FBN1 IRF5 PDSS1 CCN2 ENG STAT1 SFTPB IL12B ATP5F1A HSPG2 HLA-DRB1 COX1 PIGN CCN2 CLCN7 HLA-B TRNF CACNA1D EOGT NFU1 ND1 VAC14 TERT COL1A2 SCARB2 KIAA0319L CAVIN1 TRNW NOTCH1 COX3 FOXF1 JAK2 PPCS GBA COX7B MUC5B UBE2A RBPJ NKX2-1 GATA6 COL1A1 HLA-DRB1 COX2 CCR6 NFIX THPO ARHGAP31 HBB ND6 SLC37A4 TCIRG1 IDUA SARS2 ACVRL1 MGP DLL4 SFTPA2 ND5 KRT8 PPARG LAMB2 CACNA1D IKBKG TBX4 G6PC3 FIG4 MLX
Hypertension
Genes 410
GPC3 MPL PRKAR1A ABCG8 ND1 CYP11B1 TRNS1 B2M MMP2 BRCA2 SDCCAG8 HMBS LYZ PKD1 C8ORF37 BSCL2 WT1 SCNN1B SLC25A11 COX2 CEP19 TRNQ YY1AP1 ECE1 WT1 KCNJ5 ENPP1 FN1 PDE11A HGD SLC25A11 HSD11B2 MFAP5 GUCY1A1 DYRK1B SPRY2 SLC2A10 SMAD6 COX3 SCNN1G SCNN1B LARS2 FOXF1 NPHP4 TRNL1 TMEM67 IL12B HIRA TRIM28 MLXIPL CDH23 CLIP2 HLA-B TRNF POU6F2 NFU1 SDHC CEP290 ENPP1 EDA CYTB SDCCAG8 HLA-DPB1 SCNN1A NKX2-5 COL5A1 LEMD3 YY1AP1 TBL2 ALMS1 NOTCH3 CLCN2 ARVCF SEC24C CFH FH TGFB2 TMEM127 ARMC5 AIP SDHA JMJD1C COX1 ND5 COMT NF1 CACNA1D TGFBR1 REST LDLRAP1 GTF2I PDE3A TNFRSF11B MAT2A HSD11B2 TRNH CORIN SERPINA6 BBS10 AIP MAFB FOXE3 SCN2B SMAD4 CYP11B1 TRNK SLC52A3 TRNL1 CYP17A1 GBA SDHB BBS1 HBB CCR6 XPNPEP3 ERCC4 VHL BBS7 GP1BB TRNE OSGEP PPARG NOS3 TRPC6 HMBS JAK2 VHL KRT18 TRNS1 WT1 NPHP1 SDHD INVS KCTD1 OFD1 USP8 FIG4 TRIM28 LRIG2 PCSK9 SDHB SCNN1G CCN2 COL1A1 TRNL1 WT1 PTPN22 LDLR PRKAR1A COX1 VHL TRNC COQ7 LEMD3 PRKACA MKKS BBS5 SLC52A2 SDHD TRNW COX3 RREB1 GPR101 SMAD3 INVS KIF1B DNAJB11 COX2 APOA1 RET ARHGAP31 KCNJ5 WT1 ND5 GDNF CUL3 GLA FLT1 ACVRL1 TNFRSF11A VHL GNAS PRTN3 COL3A1 ABCC6 XYLT1 CYP11B1 ADAMTSL4 FGA C3 COL5A2 BBS9 ERCC6 KCNJ5 FBN1 APOB BAZ1B PAM16 POU3F4 TMEM70 ND4 STOX1 GNAS RFC2 TGFBR2 CALR IQCB1 CYP21A2 MMP14 SLC37A4 ALX4 TRNQ TBX1 THPO GTF2IRD1 GATA5 ND6 FN1 RPGRIP1L CFB ANGPTL6 RET XYLT2 VANGL1 NR3C1 PDE11A NR3C2 POR TRNK BMPR2 MGP TRNV SUGCT RET MYH11 PRKAR1A MDH2 FMO3 KLHL3 WNK4 TMEM237 LZTFL1 TRNK IRF5 STAT1 NSMCE2 MUC1 COL4A4 HLA-DPA1 GLA IDUA NOTCH2 TRNW CC2D2A SCNN1A NR3C1 CPOX USP8 BBS2 ELN CYP11B2 SMARCAL1 LMX1B BNC2 TRIM32 MAX MKS1 PKD2 LRP6 PRKACA COL3A1 SDHD NPHP1 MAX PRKG1 MYLK HLA-DRB1 DIS3L2 CFI LMX1B ACAT1 ELN EGFR ND6 ELP1 ELN SLC37A4 PPARG CEP164 LMNA PLIN1 DLST TP53 TRNF SMAD4 LOX UFD1 FMR1 SDHB NOTCH1 SMAD4 BBS12 IFT172 ABCG5 MYMK CFHR1 TRIP13 SLC2A10 GJA1 WDPCP FUZ CYP17A1 TRNS2 WDR35 MYH7 SDHAF2 LMNA NPHP3 GUCY1A1 EXT2 HPSE2 OFD1 LMNA FGFR2 MEF2A PLIN1 COL4A3 CEP290 ACTA2 KIF1B CD2AP TGFB3 FBN1 TRNS2 SH2B3 COL4A5 NOD2 SDHC PDE3A G6PC THBD FBN1 CAV1 TTC8 ALMS1 ITGA8 LMNA GANAB LIMK1 BBIP1 CTLA4 BANF1 CCDC28B CFHR3 FBN1 H19 CACNA1H ARMC5 AIP CCND1 ADA2 ARL6 EDA2R CBS SH2B3 TET2 CACNA1D ADA2 ND1 VAC14 IFT27 PDE8B CYP11B1 TRAF3IP1 CDH23 BBS1 TMEM127 COL4A3 GNAS ELP1 ACTA2 NPHP1 MTTP WNK1 WDR19 ZMPSTE24 CD46 GCH1 KCTD1 ADA2 ABCB6 ACTN4 NFIX ENG TGFBR3 ABCC6 WRN LMNA BBS4 PKHD1 FGFR2 MC4R ERCC8 KIF1B KRT8 TBX1 JAK2 PHF21A MLX ABCC6
Thrombocytopenia
Genes 409
ERCC6L2 TNFRSF11A MECOM SBDS NIPBL ARPC1B NFKB1 CTC1 JAK2 CASP10 TET2 ATRX TREX1 RFX5 TERT SF3B1 SBDS RASGRP1 NOP10 HYOU1 PRKCD MECOM IRF2BP2 FANCG PEPD TERC ERCC4 WAS PARN GBA TREX1 GUCY1A1 FANCF TNFAIP3 TINF2 NRAS LARS2 RFXAP MMAB IFIH1 ALG8 SLC7A7 HIRA SLC19A2 GP1BA DIAPH1 GP1BA RNASEH2C ANKRD26 TBL1XR1 DHFR FIP1L1 PRF1 HLCS SAMD9 SMPD1 CIITA RBPJ BCOR NPM1 ITK BCR JAK2 SRP54 IFIH1 XPR1 PLAU STX11 SLC46A1 DNASE1 ARVCF NABP1 CALR RAG2 GALC TNFRSF13C SEC24C CFH FANCG ITGA2 FCGR2A COG6 PHGDH TCN2 RUNX1 NUMA1 IFNG GATA1 FLI1 ELANE JMJD1C COMT CA2 HPS5 STAT3 KRAS TUBB1 ATP7B SLC7A7 ITGA2B GFI1B MYSM1 SLC20A2 CORIN VWF MPL FANCA GP1BB POMP GATA1 NHEJ1 TPP2 GBA GBA LRBA FANCB EFL1 RAD51 PRKACG PDGFB C1R MMUT GP1BB RUNX1 FANCD2 USP18 WIPF1 CD81 NOS3 ACAD9 AP3B1 PRF1 GATA2 FANCB FLI1 ADAMTS13 BRCA1 MAP2K1 RTEL1 APOE ITGA2B SPP1 CTLA4 GATA1 BRAF IL7R NPM1 ARHGEF1 MTOR XRCC2 MPL FOXP3 DCLRE1C PSMB8 PSMB4 SP110 FANCC COG4 ACTN1 SLC46A1 FANCL MYORG RREB1 C1QA ESCO2 WRAP53 RNASEH2A BTK DGKE DNAJC21 FAS TINF2 LIG4 ITGB3 CD81 FCGR2C DKC1 OSTM1 PRKCD SAMD9L GP1BA BTNL2 PTPN11 SPATA5 TNFSF12 FLT1 DLL4 ZBTB16 FASLG STIM1 RAD51C STAT5B C3 NHP2 GATA1 PRDX1 G6PC3 GP1BB ARHGAP31 GP1BA SLC35A1 MS4A1 NBEAL2 FASLG ACAD9 NFKB2 FANCD2 KIF15 APOE STOX1 RFWD3 STT3B TERT UROS WIPF1 NOP10 LMBRD1 GBA HLA-B LBR TNFSF11 SLC19A2 NHP2 VWF HOXA11 TBX1 PTPN22 STAT4 PML SCARB2 FANCI GP9 CFB LAT ERBB3 SALL4 PARN NBN TET2 ITGA2 RARA GFI1B MAD2L2 HELLPAR ICOS RFXANK GATA1 TNFSF12 USB1 CFH FAS SMARCAL1 SBDS LYST HOXA11 FANCA STAT1 PCCB SLC35A1 TALDO1 ANKRD11 SLX4 CASP10 TET2 RAG2 TERT AGK CYCS ACD TNFRSF13B GP9 KDM6A FYB1 RNASEH2A DNAJC21 SMARCAL1 VPS45 KMT2D GBA PALB2 CFI TALDO1 ABL1 HLCS CD46 FANCE FANCM FLNA CFI WFS1 LIG4 SNX10 SLFN14 PDGFRB DKC1 PNP STT3B COG1 CR2 ADA TMEM165 FARS2 ZAP70 UFD1 ETV6 STAT3 NBN GBA CFHR1 CD19 SALL4 ABCD4 TREX1 PSMB9 GP1BB RBM8A TERC RAG1 TFRC EFL1 OCLN FOXP3 FANCE CLCN7 CTC1 LYST TBXAS1 NOTCH1 MMAA DOCK6 MPL FAS TERT NSUN2 CTLA4 XIAP ITGB3 COL4A5 VPS33A PRKAR1A FCGR2B RAG1 THBD WAS TERC GNA14 BLOC1S6 RNASEH2B CFHR3 RPS19 SC5D BRCA2 WAS HLA-DRB1 IKZF1 PRKCD ACP5 MYH9 UBE2T SH2D1A TINF2 MVK EOGT CDC42 CD109 MPIG6B SCARB2 OCRL ADAR RNASEH2C SMARCD2 MYH9 CD36 NHP2 CD40LG CD46 TINF2 SRP54 FCGR2C DKC1 GATA1 PSAP NBEAL2 SAMHD1 IRAK1 DGUOK MAD2L2 MMUT NFKB1 FANCC SRC UROS BRIP1 ABCA1 SARS2 PCCA GBA MMACHC TBX1 IVD TET2 MMUT STIM1 UBE2T RTEL1 TERT SAMHD1 RBM8A NFKB2
Chordoma
Genes 3
TSC2 TSC1 IFNG
Synovial sarcoma
Genes 2
SSX2 SSX1
Renal neoplasm
Genes 167
GPC3 REST GPC3 TSC2 VAMP7 TRIP13 HNF1B BUB1B KCNQ1OT1 SOX9 FLCN SDHC TRIM37 SDHAF2 LMNA EXT2 GATA4 TSC2 BRCA2 SRC BUB1 FH APC SLC49A4 SDHB WT1 HDAC4 SLC25A11 SDHD BAP1 ALX4 SRY VHL KLLN CTNNB1 NR5A1 KEAP1 DICER1 DIS3L2 WT1 FIBP DLC1 FN1 PIK3CA NOD2 SDHC FGFR3 VHL MAP3K1 EP300 FOXE1 WT1 AXIN2 MITF PAX6 SDHD IFNG NSD1 TBX18 H19 H19 TRIM28 MDH2 PTCH1 GPC4 MLH1 POU6F2 AKT1 WT1 CCND1 ZFPM2 H19-ICR TP53 TRIP13 GPC4 COL14A1 TRIM28 VHL WT1 MET TSC1 TRIP13 AKT1 MSH6 POU6F2 HABP2 CDC73 H19 KCNQ1OT1 H19 IGF2 NRAS BUB1B KCNQ1 FLCN CDKN1B DIS3L2 CDC73 REST PRCC IGF2 CDKN1B STK11 WT1 WT1 NR0B1 BUB3 DCC WT1 TSC1 KLLN MSH2 HNF1B TSC2 TP53 SEC23B GPC3 PTEN HNF1A KIF1B MAX DICER1 PIK3CA PIK3CA DIS3L2 RNF139 MINPP1 DMRT3 BRCA2 BUB1 RET CDKN1C AAGAB TSC1 WT1 FH GPC3 WRN PIK3CA TMEM127 VHL IGF2 FLCN H19 OGG1 SETBP1 SDHB BUB1B SDHA IGF2 CEP57 TFE3 FH CDC73 GPC4 DICER1 PTPRJ LMNA HNF4A DLST H19 SDHB BMPER PALB2 FLCN PHF21A WWOX
Obstructive sleep apnea
Genes 35
AGRN SLC18A3 IDS SYT2 CCDC47 NFIX HRAS NGLY1 SLC25A1 POGZ PCGF2 DNA2 SNAP25 CHAT SH3BP2 IDUA FGFR3 EP300 TRPV4 CREBBP SKI DNA2 IDUA PLCB4 SLC5A7 GNAI3 AHDC1 COL13A1 NONO ARCN1 EDN1 VAMP1 BMP2 ATN1 MYO9A
Non-Hodgkin lymphoma
Genes 32
ATM FAS CASP10 CTLA4 FAS BCL10 CD28 BIRC3 FOXP1 TNFRSF1B MYC CCND1 ASXL1 ATM MALT1 CTLA4 CD28 SRSF2 KIT POLE IGH ADA TET2 FASLG PIK3R1 NTHL1 RASGRP1 TNFRSF1B PRKCD NBN RHOH IGH
Sleep apnea
Genes 96
SNRPN SNORD116-1 NDN CCDC47 PRPH SRPX2 CEP57 MAGEL2 FGFR2 MKRN3-AS1 SLC25A1 FGFR3 CTNNB1 RERE PCGF2 DNA2 SNAP25 RET IPW MAGEL2 SH3BP2 EP300 PWAR1 TCF4 NPAP1 SLC52A2 FLCN LARP7 FGFR3 GABRG2 SLC52A3 SYT1 GPR101 DNA2 NGLY1 PLCB4 COQ2 GPR101 MKRN3 TWIST1 AHDC1 COL13A1 P4HTM ARCN1 SOD1 GSN COLQ ASCL1 ATN1 MYO9A AGRN RUNX2 COQ2 GRIN2A NADK2 DCTN1 SLC18A3 IDS SYT2 SNORD115-1 RAI1 NFIX HRAS NGLY1 LTBP3 PRPS1 TSPYL1 POGZ CHAT IDUA FGFR3 AIP FGFR2 TCF4 TRPV4 GNE BRAF PWRN1 FGFR3 CREBBP SKI PHOX2B IDUA DKK1 COL3A1 LAMB2 SLC5A7 GNAI3 GNE RPS6KA3 NONO HERC2 EDN1 VAMP1 BMP2 NEFH
Behavioral abnormality
Genes 2136
ALG13 CACNA1A FAT4 TNFRSF11A NONO WDR45 NACC1 PRKAR1A ZMYND11 CABP4 ALS2 RHO RP1 QDPR CNGB3 CYP11B1 PIGL TRNL1 SCN9A ATF6 NDST1 GRIN2A RAX2 LMBRD1 OPHN1 SQSTM1 LMNB1 SCN1A CACNA1F HK1 NDUFAF4 SDHD NDUFB10 YWHAG LEPR OPTN SLC18A3 GBA ARL6 RDH12 NGLY1 POLG ARL3 PSAP SCN3A TAC3 TFAP2B HSD11B2 MAN1B1 PGAP1 ARL2BP GABRG2 SPG7 PRPF31 GUCA1A PPM1D PIGV TBX1 TYROBP DDC NPC2 IGF1 UNC119 DHX30 PITPNM3 HIRA MEN1 CEP57 PRSS12 MCTP2 NRXN1 CLRN1 SDHC LHX3 EXT2 HLCS SMPD1 HNRNPA2B1 TNFSF4 LHX1 TNIK BCOR NDUFS1 SATB2 KMT2E CFAP410 COASY LAMB1 ATP13A2 IL10 HLA-DQB1 ASS1 BCL11B PSMD12 NOTCH3 BMPR1A RAI1 AFF2 GPT2 AP2M1 PRPF8 FCGR2A NDUFAF2 JPH3 DYNC1I2 SUFU PSAT1 AGTPBP1 PODXL CLCN4 AP4E1 SH2B1 HPRT1 MED12 DOCK6 IL12RB1 PRNP STAG2 CERT1 NTRK1 TSHR NONO ACADS HERC2 FMN2 GNAT2 PRRT2 CWC27 B4GALNT1 CST6 CFAP410 SDHAF1 GTF2I MID2 SPRED1 SLC25A22 ST14 NDE1 TMEM106B RBBP8 DNMT3A NLGN3 RET PRPF6 MCOLN1 ZNF408 SLC6A5 IYD ERCC2 RAX2 NPAP1 PPOX MAPT HAL BEST1 SLC52A3 SDHA ND2 P4HTM ANG CC2D1A C1R DPF2 COQ2 ALG6 KCNV2 PRKN ACY1 SLC2A1 HNRNPA1 ATXN10 ADAMTS2 RORA ATAD3A CACNA1A ANOS1 SLC2A1 SEPTIN9 LRMDA CNGA3 PANK2 CLP1 TRPV4 MTHFR ATP6AP2 TRAK1 GJA8 CHST6 MAK LRIG2 GNAI3 OCA2 HARS1 HNRNPA2B1 FGF14 NHLRC2 COX15 TBP WWOX MED12 NDN FAM161A HESX1 RPS23 ABCA7 KCNA2 PCYT1A CLDN10 NDUFA12 ZDHHC9 COG4 GNB3 ALG13 SLC52A2 PACS1 EZH2 IL1RAPL1 CNGB3 TMEM106B GPR101 LHX4 ATP1A3 GTF2E2 TCF12 CNKSR2 POLR3A RNASEH2A ASH1L FGF12 TGFBR2 TWNK FBXO7 LRRK2 MTFMT SOBP CACNB4 EDNRA PRKAR1B NTRK2 TFAP2B ATCAY SCN11A MED13L GLA NDUFAF1 SETD5 DRD4 MEF2C NEK1 TBR1 ADH1B CLTC SLC1A2 GATAD2B CILK1 GLDC THRB POGZ PDGFRB SLC6A8 SYNJ1 DLD ABCC8 IL1RAPL1 NDUFB3 CCR1 SON ERCC2 NSMF SLC25A15 CLN8 CPS1 STX1B IREB2 KIF15 TMEM70 RFC2 TKT MCCC1 NDUFS3 GATM GJB6 FBP1 TRNQ RPS6KA3 PTPN22 TYR PINK1 IDS DRAM2 ALG12 CACNA2D2 ATXN7 MPLKIP KIAA1109 RLBP1 VANGL1 PTPN22 FGFR2 AGTR2 SNRPN AHR HLA-DQB1 TBC1D24 SCN2A SOX5 FLT4 ARF1 LYST SNCA CDH23 SRPX2 GPR35 HFE ANK3 MAPT TARDBP ANKRD11 CD96 FIG4 MTOR IDUA STAG2 AP4B1 PANK2 PAK3 POLA1 ATP6 TRNE MAPT MBD5 CISD2 PDGFB SGCE LSS LAMB2 COL1A1 JPH3 HCN1 GCLC SMC1A TNFRSF1A NEFH C9ORF72 SMG9 BBS2 TSC1 MICOS13 SLC25A4 VLDLR TMEM67 NPHP1 ANXA11 VCP RPGRIP1 FIG4 VAPB ACAT1 NMNAT1 ELN C19ORF12 ATXN10 TIMM50 FRA16E MLH3 NDUFV1 HTRA2 FOXP1 CERKL CRADD KMT2C ATP13A2 SHANK3 TP53 KANSL1 ALPL GUCA1A SDHB SMAD4 TNPO3 TWNK GBA SNX14 USH1G SLC13A5 ATP5F1A ATP7A TREX1 WDR4 IGF1R KRT86 AIRE SNAP25 IPW POLG2 PLXND1 HPSE2 TSC2 NDUFS7 PON1 HGSNAT SLC9A6 UCP2 ST3GAL5 DCTN1 ERAP1 SYP RPE65 PRNP RBM12 MSH6 C8ORF37 SH2B1 DCTN1 TGFBI CACNA1H VEGFC SLC45A1 DMD SLC1A3 CRX GSS KLHL7 FCGR2B HNRNPH2 CEP152 VAC14 ALMS1 TM4SF20 FTSJ1 SCN8A STS ATXN1 CHRNA7 ERCC3 PQBP1 AVPR2 FTL ST3GAL3 AHI1 GNAT2 TAF15 NDUFS3 AGBL5 EDN1 MECP2 AKT1 CNNM4 DHX38 PPP2R2B NSDHL PGAP3 CHMP2B TYROBP ERCC5 TRHR HLA-DRB1 MVK CEP250 CDC73 ND1 GABRD SEMA4A SUCLA2 GABRA5 PNKP OCRL ADAR HERC2 GNAI3 PEX14 PEX1 GNAS NKX2-1 TCF4 GNAS SEMA4A ZBTB20 PIK3CA GCH1 KIZ FGFR1 FLII FGD1 REV3L C4A ZFPM2 FKRP NFIX FA2H SPATA7 AGPAT2 RBPJ OVOL2 CNTNAP2 MEFV GYS2 PER2 PROKR2 TBP APP HTR2A ATP6V1A SYNGAP1 GBA HCN1 FTL DNM1 CIC TUBB2B GJB2 DISC2 VCP ALS2 GTF2H5 AMACR HSD17B10 AIFM1 CYP2R1 PDCD1 ALKBH8 UPF3B SLC6A1 EIF2S3 ALDH3A2 COX15 ERCC2 DNA2 TOR1A WDR26 RPGRIP1 RAI1 PARS2 PRODH POU2AF1 MCCC2 RNF168 CLTC IQSEC2 FGF14 BSCL2 VRK1 MYT1L CASR NUBPL GJB6 PROKR2 TBX1 MAOA NPHP4 IRF2BP2 PRPF4 FOXE3 KCNA1 MBTPS2 GRIA3 USP9X GNAT2 PRODH KCNJ5 HLA-DRB1 OCRL DNMT1 CACNA2D4 NLGN3 PDE11A SLC35A3 NR2E3 TSHR GLI3 CDKL5 PRCD MECP2 INPP5E PNPLA6 NHLRC1 NDUFA11 DAOA DGCR2 OPN1LW ASAH1 AP1S2 SLC7A7 MAP11 DHDDS LINGO1 ATF6 NMNAT1 IFT140 NFU1 OPN1MW CLP1 RP2 CEP78 FIP1L1 NDUFS2 PROK2 PRF1 SERAC1 TBC1D24 CNGA1 CNNM2 SMARCA2 PIGW BCKDHB NDP TYR IQSEC2 MOG AHDC1 IFIH1 SCN1A YWHAG NTRK1 TMEM216 RUNX2 SNCAIP PRPH2 DCAF17 ELOVL5 SEC24C ENTPD1 PPT1 FRRS1L CIZ1 BRAT1 SIL1 ARMC5 NUMA1 AIP KIAA1549 SLC9A7 TTC19 FLI1 GUCA1A EIF2S3 OPN1LW TACSTD2 CDKL5 FGFR1 COASY CNGA3 VCP TBR1 ZNF81 KLF13 CACNA1D PRNP NAA10 SACS ASPA METTL23 DCTN1 CXORF56 CHMP2B LTBP2 HEXA C12ORF65 XPA TBX2 RGS9 FGFR3 SNCA DEPDC5 SMARCB1 CSF1R CORIN GNS PEX6 ITGB6 PSAT1 PRDM16 SPR GNAQ LARP7 TSHR NDUFAF3 CNGB3 HADHA NKX2-1 GATA4 NAA10 STUB1 STS THOC2 GLE1 OPN1LW ANTXR1 DBH BCOR KRAS TACO1 AP3B1 MSX1 PFN1 VCP PSEN1 PACS2 EYS CHD2 CFAP43 NDUFA6 SPP1 ALG13 GBA ATP7B CARS2 XPR1 PEX1 POLA1 PHOX2B SUOX RPGR AARS2 PER3 RAPSN HCRT ADNP SETD2 TMEM231 PSAP TPO FKTN ARFGEF2 WAC TREM2 USH1C COX1 IMPA1 AIPL1 ZEB2 TK2 SLC25A1 PCGF2 NOTCH3 MAPK10 NDUFA13 PRKACA FOXE1 SLC46A1 GRN NDUFB9 RPGR RREB1 NLGN4X CACNA1A SIN3A TIMM8A MYT1 NECTIN1 HIBCH PDHA1 SETD5 SYT2 RET CUX2 ACSL4 FRMPD4 PIGY RRM2B ECM1 SLC45A2 NLRP1 CHI3L1 TMEM126B TH EIF4G1 COX10 PHGDH FLT1 FBXO31 TSPAN7 VPS35 DLG3 APP CDC73 CLCNKB SKI TREX1 COL3A1 CACNA1A LARP7 APC2 DYRK1A GRIK2 ADH1C HCN1 NDUFA1 NSD1 CSNK2A1 ZFYVE26 NDUFA4 NPHP4 BCKDK AFG3L2 UBE2A ZNF41 HNF1A PRPH GM2A TBP FGFR3 HTR2A MED25 IFT88 TARS1 UROC1 GLUD1 RPGR ND4 GNAS NEK2 DBT UBA5 PRKCG RNF216 RHO SLC25A13 ITPR3 TRNS2 BPTF GBA DLG3 SLC33A1 FOXG1 ASCL1 AGRN GABRA1 TBX1 NADK2 GTF2IRD1 RAI1 TRNN PML PANK2 ARX PRPH2 ARG1 NDST1 KRAS SOD1 NDUFS7 SATB2 LRRK2 MECP2 PITPNM3 NTRK2 ZFYVE26 TNFSF15 HDAC8 TOR1A AIMP1 APP NOTCH2NLC PDGFB NKX2-1 BRAF RORB DMPK MAPT NAGA BMP4 GJC2 SETD5 HPRT1 SLC20A2 AGA ADNP TMEM237 ABCC8 NDUFAF4 GRIN2D CCDC47 WDR45 CDHR1 HLA-DQB1 COG5 HNMT JRK SLC18A2 NPC1 CPOX USP8 PGAP2 CYP11B2 EIF2B1 ATXN3 CYP27B1 COX7B CTNS AP4E1 AIFM1 CLCN2 MYORG SDHD MAX ZNF423 KDM6A HESX1 CRYGC POLH HNF1B TCF4 SLC22A5 IL12A SLC18A2 PDHA1 SLC25A19 AP1S2 PEX26 ELP1 PNP DDB2 SLC2A3 PRPS1 ACADL ARG1 MOG ARNT2 ARHGEF6 RAC1 POLR3A UNC13A GPR143 NDUFA13 SMAD4 RAB28 ADCY5 NDUFB11 RPS6KA3 PEX3 DEAF1 EGF NDUFAF3 SLITRK1 EIF2B5 PTPN22 SRPX2 DHTKD1 AARS1 SDHC RNF13 C12ORF4 NLRP3 MAGEL2 ADAM9 PRPH2 VPS13C SPART FTSJ1 VCP KCNQ3 SORL1 FANCE DNA2 GPR143 IDH3B LYST PIGL RTTN FGFR1 CRKL CYP27A1 PLA2G6 NLGN4X ABCA4 HCRT ATXN3 DCTN1 CHRNA2 HESX1 SLC24A5 HIVEP2 PIGO NOD2 NDUFA10 SHANK3 PSEN1 PIK3CA NR2E3 SYN1 NAA15 TSHB TCF4 GAMT NDUFV1 MEF2C NSD1 SPR SEPSECS KCTD17 SMC1A MCOLN1 PAH PGK1 LIPT1 SCN8A NDUFS8 STAT4 GRIA3 IKZF1 SLC35C1 MKRN3-AS1 AHSG PLEC VPS13A RAD21 CDC42 ADA2 ATXN8OS IMPG2 HNF4A CACNA2D4 ATP1A1 MAPK1 SETBP1 KCNJ2 NDUFA9 CYP27B1 CDH23 EPCAM PDE6H GABRG2 EFHC1 ELP1 SLC6A8 PRNP PEX16 KISS1 APOE SLC3A1 MMADHC SZT2 PRRT2 PCDH15 WHRN FRMPD4 NOP56 ND3 ACTL6B ST3GAL5 IRAK1 DDB2 C9ORF72 ELP2 SARS1 TCF20 BCR MECP2 ALS2 SLC7A14 UQCC2 MC4R KCNAB2 KCNB1 CUL4B ARHGEF18 IRF5 DNMT1 CP GNE DDX11 ATRX NDUFS4 IKBKG SAMHD1 CNGB1 ATRX AVPR2 IDH3A GRN ZNF408 ARID1B AP3D1 HNF1B KCTD17 SLC1A3 CUX2 PCARE CYP27A1 ATXN3 TP63 GFM2 OPA1 MBTPS2 GPHN SNCA APOL4 CTSH DRD3 ADH1C MITF TTC8 EML1 PROM1 GPC4 HMBS TREX1 POU1F1 FGFR1 SLC18A3 GPR101 PDE6H ZSWIM6 GABRA2 SLC25A11 SUCLA2 PON2 SNCA ADGRV1 COL17A1 GRIN1 PCSK1 HMGCL BCKDHA PNPLA6 GLS ECE1 IGF1 PMM2 NPHP3 APOL2 DNAJC6 SYN2 TAT OTUD6B WDR73 GNAO1 HTT ACTG1 NDUFAF5 CBS SEMA4A ERCC4 FGFR3 CAMTA1 AMER1 SDHA NDUFV2 PREPL IRF6 WFS1 CACNA1G FUS NKX2-1 POC1B GPHN ALDH18A1 CHST6 LRAT GRIA4 ERCC6 NUS1 LEP TMEM240 KAT6B PUF60 MANBA CNTNAP2 TRNF TBL1XR1 PEX5 HTT UBE3A DOK7 MSTO1 EP300 CHD1 ATPAF2 PDE4D SLC6A4 PDGFRB UCHL1 ESS2 GABRG2 SASS6 PRNP PDE6C TYR KISS1R MFSD8 TINF2 RSPRY1 VPS53 RTN4IP1 AP1B1 OTC DUOX2 PSEN1 PTEN SCN2A HLA-DQB1 SLC46A1 CPOX ST3GAL5 SLC6A17 SLC6A19 RAB11B LINS1 SNORD115-1 GBE1 SPIB ARVCF RLIM KDM5B DGCR6 AIFM1 MST1 B3GALNT2 TMEM237 POMGNT1 AQP2 PIGV SYT14 TMEM127 ATRX IDUA HAX1 PEX13 SDHA MAB21L1 ZC3H14 PEX12 JMJD1C TRNS1 ND5 MMEL1 AVP TMLHE EDC3 SLC6A3 NAGA SLC5A7 POLG SHROOM4 SLC25A20 GPT2 SOX2 ATP7B GJA5 GRN SIM1 GJB2 FOXC2 PMS2 PRNP MAPT MPLKIP PROM1 AIP RUSC2 ITPA PRPH2 EZR DUSP6 EEF1A2 BCS1L SLC26A4 C19ORF12 MTHFR SDHB NGLY1 POLG PIKFYVE NSD1 ARCN1 VHL AUTS2 HNF1A DSG4 CLN8 CACNA1B PEX10 AP4M1 ND1 MSH2 NPHP1 CFAP410 HMBS NEUROD2 SPG11 C8ORF37 GNAS C9ORF72 KIF14 DUOXA2 NDUFAF5 SMPD1 VCP CTLA4 POMT2 SDHD CHCHD10 RAI1 NPM1 RPS20 USP8 SYNGAP1 ERF MEIS2 TTC8 LHCGR DPYD POLG IL6 HSPG2 NEXMIF SGSH GABRB2 NRL C12ORF4 ASL RERE DGCR8 ALDH18A1 CTNNB1 ATXN8 SGCE NEXMIF SIGMAR1 FTL GLRA1 HLA-DRB1 COX3 DAO LIAS POMT1 PLCB4 GUCY2D NUS1 AMT RIMS1 PSEN2 HLA-B NKX2-5 COX2 ARX PAX8 TRAPPC9 EEF1A2 RRM2B FMR1 MC1R SLC9A6 TRIM8 POLG ERBB4 ACTB ENTPD1 SLC2A1 ZBTB16 SPG21 MBD5 FOXRED1 GNAS ALG1 ERCC3 SLC52A2 IFT172 BCOR SLC5A5 STAT5B EPM2A BMP2 NEFH CNKSR2 GBA RPGR SNORD116-1 DHDDS OTX2 RTN4R EPG5 SETD2 GRIN2A SCN8A KCNA2 TREM2 UBQLN2 PSMD12 TREM2 PDE6B ASPA STOX1 CA4 PLA2G6 HDC HTR2A EEF1A2 CLCN4 PLA2G6 HLA-B VDR TARDBP HLA-A GSN PCNT LEP ATN1 CRB1 NDUFS4 XK TWNK PTS NDP SIK1 SLC25A20 PIGL SIM1 STAT4 MECP2 NHLRC1 TLK2 GNRH1 TRIO LTBP3 PHIP PRPS1 PSAP PTS WDR62 RPL10 CDH15 EBP EPG5 ARSA NR3C1 PDE10A ADAT3 SCN1B AP2S1 DLAT NAXD LRPPRC ABAT MAPT TREM2 SLC25A12 PIGY CACNA1C DNM1 PIGC CTNNB1 KIF11 PAH SCN2A CLDN16 TMCO1 ATXN2 TMEM106B ELN CLCN4 KMT2A FLCN EIF2B3 MATR3 DYM GABRD SNCA SYT1 NAGS LEPR TUBB2B NAGLU PRPF3 TNF SDHD PUS7 PDGFB CC2D1A CACNA1F SLC19A3 HDAC8 PRDM8 CRX CRX HTT IL23R POLG HCCS GABRA1 TAF1 NFIB ND6 SLC39A4 CLRN1 KYNU CNGA3 MECP2 TOPORS TMEM240 USH2A ATP1A3 TG SOX5 DLST DDX3X TYR UFD1 ALG11 ZNF365 STAT3 GABRA2 PRNP NBN ATP1A3 CAMTA1 NAGS GNA11 KCNJ10 CLIP1 SDHAF2 SNCB NF2 CASK AP3B2 KPTN HLA-DRB1 EHMT1 PRNP TAF1 FMR1 MAPT TMEM231 EPHA4 ARV1 KRT83 MECP2 OPN1MW ALS2 TRRAP DGUOK MC4R ARSA SARS1 POLA1 CHMP2B TP63 SDHC PARK7 PRKAR1A ASPM PSEN2 ATP2A2 KRT12 CHAT CISD2 DCHS1 TBC1D7 POLR3B GJB1 DNAJC12 RAC1 PEX11B RPE65 PPARGC1A GCSH RNASEH2B KMT5B IDUA AVPR2 PDE6C NAT8L MFRP ARMC5 HCN1 SLC12A3 PDE4D COX7B DPAGT1 COL1A1 GRIN1 KMT2A PROP1 TBK1 TTLL5 MAGEL2 WARS2 CBS EPM2A AFF2 IQSEC2 CNNM4 ARSG SH3BP2 PDE10A PWAR1 ABCA7 PC ALS2 TECR TANGO2 UBE2A ADGRV1 NLRP3 CSNK1D PNKP XPA UBAC2 SDHB WFS1 CNKSR2 FGF17 HBB MERTK PET100 CTNS JRK KCNJ11 CXORF56 CRBN PPP2CA SMARCA2 GRIN2B RGS9BP PDE6G SAG RAB39B LMAN2L HARS1 VCP XPC UBE3A TBK1 ITPR1 FBP1 POLH HCFC1 TIMM8A PDE6A GATAD2B OPN1MW STXBP1 CSF1R TBC1D24 CHMP2B DNAJC13 FUS NIPBL XPC SLC16A2 KDM5C CA4 GABRB3 IQSEC2 CPLX1 MKRN3 FUS CEP290 SCN1A SNRNP200 MUSK ZBTB11 SOD1 SURF1 DHCR7 COLQ MYO9A EYS HOXA2 GABBR2 SLC19A3 DPP6 UBA5 SURF1 DNMT1 GABBR2 HNRNPA1 KRT81 BCS1L DRD2 TSHR SPART ITM2B FGFR3 CUL4B SPRY4 TUSC3 SARDH DKK1 RLBP1 SDHA RDH11 SMARCB1 GLRX5 C9ORF72 GCDH HECW2 IFIH1 C9ORF72 SLC6A19 PRRT2 MLXIPL C9ORF72 CLIP2 NFIX PLCB4 LINS1 REEP6 LARGE1 SH2B1 PAX8 KCNT1 SHANK3 PAK3 PIGP GNRHR RSRC1 COQ2 HS6ST1 ATP13A2 APP NSUN2 CLN3 TBL2 ALMS1 DNASE1 EMC1 PTCHD1 DPYD PPOX SH3KBP1 STXBP1 IL12A-AS1 NABP1 AP3B2 RARS1 POMC GUCA1B FH ZNF365 HSD17B10 PSEN1 ARID2 NDUFS1 AUH PSEN1 MED23 MBOAT7 GNE MED12 GJB2 LAMB2 COMT DEAF1 SKI ATP13A2 DCPS TRNL2 PTCHD1 KNL1 PPP2R2B GJB6 ALDH5A1 SLC7A7 NUP88 TACR3 MGAT2 TWNK MTPAP DHPS MEIS2 TRNH SLC35A3 PIEZO2 FGFR1 KCNQ2 GABRG2 CASR PDE10A RSRC1 APP FGFR3 PACS1 TRNL1 PSEN1 TUB CPT1A TTI2 KMT2A DRAM2 TREM2 NDUFS1 GABRD GP1BB VPS13A RP9 ZDHHC9 ARSA NR4A2 MRPS22 WASHC4 NDUFS4 PRDM8 DCAF17 NHS RBP3 CACNA1G MYO7A PINK1 POLG SLC24A5 FARS2 TRNS1 TDP2 TYR TK2 RNF125 PCDH19 NDUFA6 GK AKT1 SLITRK1 FOXC2 TP63 CHD2 IMPDH1 CTSF NIPBL VAMP1 SCN1A KCNJ13 SCN2A KCNJ1 MAPT NHS ST3GAL3 NDUFS6 STX16 CHD8 LAS1L NKX2-5 P2RY11 TCF4 SPECC1L SLC1A4 TRNW CHCHD10 GRIN2A PCDH19 C1QA C9ORF72 TIMMDC1 IL12A KLRC4 RPIA KIF1B CTCF FOXRED1 ALG3 USP9X TUBB3 CKAP2L PRPS1 ACSF3 PRPH2 PDGFRB POGZ ERLIN2 MAPT PON3 MTPAP GLE1 WARS2 CREBBP NDUFAF2 RPS6KA3 ANK3 AP1S2 GABRB3 ATF6 ZC4H2 OFD1 PMPCA SYN1 PRKAR1A HCRT CHD2 ABCA4 KCNJ5 PRPH BAZ1B EHMT1 COA8 ECHS1 BSCL2 BCORL1 COL1A2 SQSTM1 PMP22 WFS1 MRE11 MED12 RGR AASS ALDH5A1 ERCC2 KCNQ3 SPAST SMARCC2 RERE SLC2A1 MAPK8IP3 PRPH2 ATRX GABRA1 FGF8 SCAPER EIF2B2 CLN6 GDAP2 PSEN1 SCN9A AQP2 TIMM50 IBA57 FAN1 PIGQ GLT8D1 NECAP1 CRBN SMC3 CC2D2A GLUD2 ABCA12 TRIP12 GCH1 AUTS2 RARA RNF113A ALG11 SQSTM1 ARSA CRY1 SQSTM1 GRN TBC1D24 PWRN1 IFNG SCN8A TWNK KDM6B DNM1 CEP78 MDH2 PIGP PRODH FMO3 PCNA SLC39A4 NLRC4 USP27X CTNS PCCB CYFIP2 HPS6 PIGH CDHR1 MAOA DEAF1 MAN1B1 NEUROD2 TSC1 GNB5 NDUFS2 UPF3B KCNT1 MAN1B1 PTEN KDM5C ALAD L2HGDH ALDH3A2 ROM1 MAPT AP4S1 TWIST1 PARK7 WNT10A COG4 HLCS CCNF NAA10 DNM1L SLC1A2 ITM2B LRAT WFS1 NSDHL TARDBP LIG4 SRY MAPT SLC45A1 TSPYL1 TSEN54 WDR11 HDAC8 HGSNAT ADSL NALCN DNAJC6 MBTPS2 USP27X HNF4A FMR1 FMR1 PMS1 TCN2 TBX4 TMEM138 CHD7 SNRPN USH2A AHCY TSC2 GUCY2D HMGCL C8ORF37 GLRB NDUFA2 FGFR2 OTUD6B FUZ TREX1 MLH1 STXBP1 ATXN8OS GDI1 PCDH19 EIF2B4 SLC19A3 SEMA4A TGFBI GM2A PDZD7 DDX3X ABCD1 HDAC4 NFIX SLC5A2 FBXO11 EP300 MYO7A HTT DNAJC5 NDUFAF6 PEX2 GRIN2A CHMP2B NSUN2 ZNF513 ATP13A2 TRNS2 SCN1B MFN2 GNAO1 RNF135 SLC2A1 NDUFV2 SLC25A1 POMC RDH5 SIN3A LIMK1 MYOD1 MED12 POMT1 FAS CACNA1A DHCR7 TULP1 MBOAT7 ELOVL1 TRIO DPYS SPG21 AP4M1 TLR4 SLC12A6 ACOX1 TREM2 SLC12A3 TBK1 TBX1 ZNF711 ASXL3 PPP3CA ATXN2 TOMM40 CHRNA7 RNASEH2C GIGYF2 PGAP3 KLLN ATAD1 SLC25A19 COL13A1 DRD5 ESR1 SEC23B POMK NFASC COMT CIB2 ADA2 BCAP31 HRAS SEMA3E SAMHD1 FOXP2 COMT PEX19 NRXN1 GUCY2D CHD7 NDUFB11 PDE6C SOX3 GABRG2 GFM1 SDHB LAS1L PCCA CFAP43 TBC1D23 CDHR1 MSTO1 ACSL4 TBX1 PLCD1 FSCN2 RPGRIP1 FGD1 NDUFS8 SNCA
Acute myeloid leukemia
Genes 50
KIT DDX41 SBDS LPP ETV6 DNMT3A TERT JAK2 NUP214 CEBPA BRCA2 TCIRG1 DNAJC21 TET2 FLT3 TET2 JAK2 SRP54 SF3B1 SRP54 SH3GL1 KRAS EFL1 PIGA MLLT10 SRP54 DNAJC21 DKC1 RUNX1 RUNX1 MPL CBFB NSD1 THPO ELANE NPM1 ASXL1 CHIC2 MLF1 DNAJC21 ERBB3 GFI1 GFI1 SRSF2 KIT PICALM RPS14 GATA2 SBDS TET2
Lymphoma
Genes 133
ATM KRAS CD19 IGH DDX41 BCL10 BIRC3 FOXP1 MS4A1 TP63 RAG1 LIG4 NFKB2 MSH6 TERC RECQL4 NTHL1 WIPF1 CTC1 LYST NOP10 RASGRP1 TNFRSF1B XRCC4 PRKCD NHP2 MAGT1 TNFRSF13B IGH RMRP RUNX1 CTLA4 DCLRE1C FAS ICOS RNF43 NSUN2 XIAP IL7R CASP10 BCL6 CDKN2A ATM IL2RG RTEL1 PARN NBN KIT TNFRSF13C TCF4 ICOS TNFSF12 CHEK2 USB1 CD19 CR2 NRAS MSH2 WAS BCL10 CASP10 MYD88 COL14A1 PRKCD TNFRSF13B MYC MDM2 SH2D1A CCND1 BCL10 CFTR CD27 PGM3 TCF4 CHD7 IGH LIG4 BLM BCL2 TET2 HLA-DRB1 PRSS1 NPM1 KIF11 ITK WRAP53 RAD54B TINF2 FAS DKC1 APC CD81 LIG4 BLM CD28 DKC1 AAGAB RAG2 TNFRSF1B MLH1 TNFRSF13C DNASE1L3 NFKB1 PMS2 ASXL1 IL2RG PRF1 PTEN MALT1 RAD54L CTLA4 CD28 PNP SRSF2 TNFSF12 STAT3 POLE ADA CR2 ADA FASLG PIK3R1 TP53 CTRC ZAP70 MYD88 RB1 RMRP SPINK1 TERT KLHDC8B NBN RHOH
Atherosclerosis
Genes 88
SMPD1 LDLRAP1 LDLR ACTA2 CYP7A1 ANTXR1 GLB1 FBN1 APOE APOB MAT2A ABCG8 ZNF687 LMNA AGPAT2 NPC1 LMNA GGCX FOS GGCX AGXT LMNA FOXE3 CAVIN1 SERPIND1 SMAD4 TGFBR2 SMPD1 APOB SMAD3 MYH11 CAV1 LMNA ACTA2 ABCG8 TNXB CYP27A1 COL3A1 ZMPSTE24 TGFB3 PRKG1 MYLK CEP19 LMNA ALMS1 LDLRAP1 CSF2RA APOA5 NOTCH3 ESR1 LCAT ABCA1 KCNJ5 MYH11 CSF2RB ENG TGFBR3 TGFB2 SC5D ABCC6 WRN ENPP1 HGD ANGPTL6 ELN XYLT2 LMNA ABCA1 BSCL2 LIPC PPARG SMPD1 LMNA LCAT MFAP5 ABCA1 BANF1 LMNA LOX MYH11 ABCC6 PPARG LOX XYLT1 PCSK9 NPC2 TGFBR1 ABCG5
Apnea
Genes 319
ACY1 KCNQ2 SNORD116-1 ND5 PLAA CPLANE1 PRPH NDUFA4 PDE6D TRNW ECHS1 ND6 COX15 DNA2 KIF7 CHRNE TRNV ND4 NDUFS8 ARL3 SLC2A1 NDUFAF3 TCTN1 MCCC1 NDUFS3 GPR101 MKRN3 GLRA1 CEP290 GBA CSPP1 SOD1 SURF1 GSN COLQ FBP1 PCK1 ASCL1 ATN1 MYO9A NDUFS4 AGRN TMEM216 TRNQ ASCL1 GABBR2 SLC19A3 GDNF SLC25A20 NADK2 SLC18A3 HMGCL SCN4A RPGRIP1L IDS SLC39A8 NGLY1 LTBP3 CC2D2A PRPS1 NDUFS7 MECP2 HTRA2 TECPR2 FGFR3 INPP5E FGFR2 TSEN54 BRAF PWRN1 FGFR3 ND2 DKK1 MKS1 WFS1 INPP5E PLPBP EDN3 RPGRIP1L SURF1 PCCB AMER1 TRIP13 CCDC47 CEP57 PHOX2B CLCN7 PTF1A CTNNB1 BTD TRNF PLCB4 BTD NDUFS2 EP300 OFD1 BUB1B OPA1 PSAP FLCN TMEM67 GABRG2 SYT1 NDUFS2 COQ2 KAT6B BUB3 NDUFS1 TWIST1 HYLS1 AHDC1 CEP104 TMEM216 RET RUNX2 ZNF423 TCTN3 SNORD115-1 RAI1 CSPP1 PIBF1 TSPYL1 PDHA1 MKS1 TSPYL1 MYO9A FAM149B1 TMEM237 NDUFAF2 BRAT1 ND6 SCN2A NDUFS1 IDUA AIP SKI GNE ACADSB CEP41 ND5 ECHS1 GPHN LAMB2 SLC5A7 CTSD KIF5A ALPL RPS6KA3 NONO HERC2 LIFR BRAT1 NDUFA11 TMEM138 CC2D2A SNRPN LIFR TMEM67 TNFSF11 SRPX2 KIAA0586 ATP5F1A NDUFA2 RPGRIP1L FGFR2 KIAA0586 FGFR3 TRNH SNAP25 RET RARS2 ND3 IPW MAGEL2 SCN5A SLC6A5 BUB1 INPP5E NPAP1 TCTN2 LARP7 FGFR3 B9D1 NDUFV1 SLC52A3 TRNL1 DNA2 PRNP ND4 NGLY1 CEP120 PEX5 SDHA INPP5E P4HTM ARCN1 SLC18A3 NDUFAF6 ABCA3 NDUFA2 ARMC9 COQ2 GRIN2A TMEM237 DCTN1 SFTPB TACO1 HSPD1 KIAA0753 NDUFAF2 TRNS2 CEP290 SCN4A SNX10 CEP41 PIBF1 NDUFA10 NDUFV2 CHAT CISD2 NDUFAF5 FARS2 TRNS1 KIAA0556 NDUFB8 CHAT RNF125 TMEM107 TCF4 NDUFV1 TRPV4 TOE1 PHOX2B IDUA GNAI3 TRNL1 EDN1 VAMP1 TMEM231 CPT2 DPAGT1 ND1 LIPT1 HSPG2 NDN COX1 MECP2 FBN1 KIAA0586 MAGEL2 CEP120 TMEM216 MKRN3-AS1 SLC25A1 SLC5A7 RERE PCGF2 NDUFA12 AHI1 NDUFA13 ND1 GLUL TMEM237 SH3BP2 D2HGDH SCO2 PWAR1 TCF4 AHI1 ARMC9 SLC52A2 GNAI3 NDUFA9 NEK1 TRNW COX3 RBM10 SLC6A9 LIAS GPR101 AHI1 PLCB4 TRNK COL13A1 COX2 SOX9 MTFMT PDHA1 TECPR2 SYT2 NFIX HRAS PLAA POGZ NPHP1 DST PET100 TCIRG1 PCCA NEB GBA CEP57 CPLANE1 FOXRED1 TBR1 CRYAB ATP6 CREBBP SKI PEX13 ARL13B COL3A1 GNE ZC4H2 CSPP1 FBP1 BMP2 NDUFS8 NEFH
Small cell lung carcinoma
Myeloid leukemia
Genes 20
KIT SETBP1 NF1 ARHGAP26 CBL TET2 KRAS PTPN11 F13A1 SAMD9L SAMD9L GATA2 CBL ASXL1 DNMT3A F13B NRAS SRSF2 TERC TERT
Anemia
Genes 722
GTF2H5 PIEZO1 ERCC6L2 TNFRSF11A HBA2 MECOM RPL18 EPHB4 SBDS RPL35A BIRC3 FERMT3 COX15 ATRX OPA1 NFKB1 CTC1 JAK2 CASP10 NLRP3 TET2 TYMP GREM1 ZBTB24 ATRX LAMA3 FAM111A RFX5 SLC40A1 RMRP SF3B1 SBDS HBB RASGRP1 KIT HYOU1 CASR PRKCD ENG SURF1 HBB HBA2 COQ2 PIGA NPHP4 SLC19A3 IRF2BP2 HMGCL FANCG TNFRSF4 PEPD CA2 EPB41 HBA1 TERC ERCC4 ABCA1 WAS MARS1 REN KLF1 TCIRG1 BMPR1A HBB PARN GBA COX6B1 ENG COL7A1 PLA2G4A TBCE IFNGR1 PKLR RPS14 FANCF RPL15 TNFAIP3 TINF2 NRAS LARS2 WFS1 RFXAP ADA2 RPS7 IL2RB SURF1 COX8A MMAB RPS7 IL12B RPS17 SMAD4 ALG8 SLC7A7 SLC19A2 SLCO2A1 HLA-B CD3G ORAI1 TBL1XR1 DHFR STEAP3 FIP1L1 SLC4A1 SPTA1 COX14 PRF1 AGXT TF COL7A1 SPTA1 SAMD9 ABCD3 KCNN4 PGK1 NDUFS2 CIITA SEC23B BCOR NDUFS1 PET100 NPM1 ITK SRP54 BPGM STX11 SLC4A1 SLC46A1 DNASE1 COX20 PLEC PLEC RPS28 NABP1 CALR CLCN7 RAG2 CDAN1 PHKG2 TNFRSF13C HBG1 CFH RPL31 FANCG FCGR2A IL2RG NDUFAF2 COG6 CCND1 SLC11A2 PHGDH NUMA1 IFNG SPTB ITGB4 RPS26 GATA1 HPRT1 ELANE RPS27 SLC29A3 ISCU MMP1 HELLS CA2 FLI1 SPTB STAT3 POLG KRAS RHAG SPTA1 STIM1 ATP7B SLC7A7 ITGA2B RPL11 SHPK HBB-LCR GP1BA FOXP1 EPB42 COA8 GYPC MYSM1 MPL RPS26 FANCA LAMB3 ALAS2 ACVRL1 MPLKIP AMN ABCB7 GATA1 NHEJ1 TPP2 GBA HBB LRBA DNMT3B SDHA ALAS2 CP FANCB EFL1 FECH RAD51 PRKACG C1R MMUT RMRP DBH FANCD2 PFKM CLCN7 SMAD4 TACO1 XRCC4 LCAT NPHP1 PRF1 NLRP3 SMAD4 SNX10 TTC7A FANCB RPL5 ADAMTS13 BRCA1 COL17A1 RTEL1 AMMECR1 PACS2 FASTKD2 ALAD AK1 HBB NDUFAF5 SMPD1 SPP1 HBA2 NDUFB8 IDH1 HBB ATP7B CTLA4 GATA1 GATA1 CAD NPM1 SPTB SLX4 XRCC2 FTCD MPL SRD5A3 FOXP3 CD59 NHLRC2 DCLRE1C PSMB8 PSMB4 GCLC KIT MTR TMPRSS6 SP110 SMAD4 HBA1 RPL5 NDUFA12 EWSR1 NDUFA13 PGM3 FANCC IDH2 SLC46A1 LPIN2 FANCL TP53 UNC13D AGGF1 STK11 GTF2E2 C1QA TGFB1 RPL35 APC GSS GPI WRAP53 BTK DGKE PDGFRA DNAJC21 FAS SCO1 MTFMT TINF2 ABCB7 RPS29 ITGB3 CD81 EPB42 DKC1 OSTM1 STK11 IFT140 PRKCD RPS19 SAMD9L BTNL2 SPTA1 COX10 RPL15 NLRP1 HBG2 NLRC4 RPS15A CRIPT SDHA PHGDH GLA TNFSF12 ACVRL1 ADA SPTA1 ZBTB16 FASLG CTSK STIM1 FOXRED1 KLF1 COL7A1 CLCNKB SFXN4 HBB COX4I2 SLC25A13 RAD51C DNAJC19 RMRP ANK1 STAT5B C3 GATA1 PRDX1 G6PC3 COL7A1 RPL35A YARS2 DDX41 BCL10 NDUFA4 NPHP4 ERCC2 AK2 CLPX HBA1 COA8 ECHS1 RPL11 MS4A1 FASLG LIG4 TFR2 NFKB2 FANCD2 PUS1 TBXAS1 TARS1 AASS IREB2 KIF15 RFWD3 ATRX TERT NDUFAF3 PLEKHM1 HBA1 PTEN UROS WIPF1 HBA1 ATRX NDUFS3 RHAG NOP10 LIPA LMBRD1 THRA GBA TRNT1 HLA-B HBD TACO1 IRX5 RPL27 SEC61A1 TNFSF11 SLC19A2 HBG1 NHP2 PCNT ALX4 BMPR1A NDUFS4 PTPN22 TRNN CD55 STAT4 HK1 PML ANK1 FANCI NT5C3A BMPR1A UMPS NDUFS7 G6PD CFB LAT LYRM7 ERBB3 PARN NBN HSPA9 TET2 RARA LARS1 RNF113A MAD2L2 HELLPAR TEK ATP11C BRCA1 ICOS RFXANK ELMO2 GATA1 TNFSF12 ELANE PTH1R GLRX5 USB1 EPO CFH FAS SMARCAL1 SBDS LYST HPRT1 FMO3 RPL26 TTC7A ENG FANCA STAT1 MUC1 PCCB TALDO1 HPGD SLX4 CASP10 TET2 RAG2 TERT SLC4A1 MYD88 GLA PKLR ACD TNFRSF13B KDM6A CLCN7 PTF1A ACVR1 RPS10 HAMP SAMD9L FARSB CPOX RPS10 NDUFS2 DNAJC21 SMARCAL1 VPS45 KMT2D TGFB1 GBA PALB2 CFI GCLC PUS1 TALDO1 HBB SRD5A3 PIGT CD46 FANCE FANCM TMEM67 SLC4A1 NPHP1 DNM1L SLC2A1 RPL26 CFI WFS1 RAG1 LIG4 UMPS CASK PGM3 ADAR PSMB8 PDHA1 SNX10 MTRR DKC1 PNP WT1 HMOX1 COG1 CR2 STEAP3 ADA COL7A1 FARS2 LAMC2 ZAP70 CUBN ALPL F2 ETV6 TCN2 STAT3 NBN RPS15A CFHR1 GDF2 ITGB4 CD19 HMGCL UROD TNFSF11 MMADHC TCIRG1 FECH NDUFA2 ABCD4 TREX1 RAG1 PSMB9 COL4A1 CDCA7 TF RBM8A KRT14 SDHC TERC EXT2 LPIN2 RAG1 TFRC EFL1 TSR2 PFKM HBB RPS29 FOXP3 FANCE CLCN7 CTC1 SDHB LYST KIF1B PNPO TBXAS1 HAVCR2 ABCG8 MMAA NDUFAF6 TRNW FAM111A DCLRE1C FAS HBB TERT RPS27 NSUN2 CTLA4 XIAP PLEKHM1 IL7R NOD2 GSS VPS33A HBG2 NDUFA10 PRKAR1A FCGR2B EPB41 RAG1 NDUFV2 HBA2 THBD CISD2 ERCC3 TERC NDUFV1 SLC4A1 GNA14 GALT SLC2A1 ZBTB20 CFHR3 TRNS1 RPS19 STAT1 ANK1 BRCA2 AIRE RPL27 SLC25A38 WAS IL2RA PGK1 HLA-DRB1 LIPT1 HBB RPS24 FDX2 ALDOA IKZF1 PRKCD RPS24 LAMA3 ATRX KCNQ1 DAXX UBE2T SH2D1A SLC12A3 ACAD8 MVK DNAJC19 MTHFD1 UBR1 ADA2 RHAG LAMC2 SCO2 MPIG6B SCARB2 CHD7 IGH OCRL NDUFA9 ALAS2 C15ORF41 RPS14 GPX1 SMARCD2 STING1 HBA2 CD40LG CD46 CBLIF TINF2 SRP54 DKC1 TPI1 ABCB6 GATA1 ACTN4 RECQL4 PSAP RAG2 IRAK1 BMPR1A HBB MAD2L2 NFKB1 PET100 FANCC TSR2 MALT1 UROS BRIP1 FANCL PHKA2 TCIRG1 YARS2 ABCA1 SARS2 MTRR FERMT1 RPS17 PCCA PNPO GBA MMP1 TRNT1 APOA1 MMACHC CP LAMB3 TET2 RPS28 MMUT STIM1 UBE2T RTEL1 RRM2B KIF23 TERT KCNE1 NDUFS8 PHF21A MLX
Hypercoagulability
Genes 19
PROC SPTA1 SPTB F5 MYD88 EPB42 SLC4A1 PROS1 AGGF1 HRG PROC GATA2 THBD PLAT ANK1 PROS1 F9 DLD PIGA
Portal hypertension
Genes 62
CLDN1 TMEM67 GDF2 MPL HLA-DRB1 SHPK F5 GBE1 SP110 MLXIPL ARHGAP31 JAK2 TET2 CC2D2A EOGT FARSB ADA2 JAK2 ACVRL1 NEUROG3 GLIS3 POU2AF1 GDF2 STN1 DLL4 NPHP3 RBPJ TCF4 INPP5E NOTCH1 IL12A PIGM DOCK6 RPGRIP1L SMAD4 SPIB ELN CALR DGUOK DGUOK RPGRIP1L MST1 DCDC2 BTNL2 PKHD1 TET2 ALMS1 TNFSF15 DLL4 SLC30A10 IL12RB1 IRF5 MMEL1 ITCH MPL GPR35 ENG TMEM67 JAK2 CC2D2A TJP2 TNPO3
Splenomegaly
Genes 478
CLDN1 MPL PIEZO1 TNFRSF11A GUSB CCDC115 FERMT3 AGPAT2 B2M JAK2 CASP10 NLRP3 ATRX LYZ IDUA SF3B1 RASGRP1 CASR PRKCD HBB HBA2 KCNN3 LMNA MPL MPL RPGRIP1L TNFRSF4 PEPD EPB41 NGLY1 IFT172 ABCA1 KLF1 GPC1 GBA HSD3B7 TREX1 SUMF1 IFNGR1 PKLR NRAS IL2RB NPC2 TMEM67 CYP7B1 IFIH1 ASAH1 HIRA GBA SLCO2A1 GNPTAB BRAF TP53 BMP2 DHCR24 LMNA CYBA STEAP3 KCNH1 USB1 SPTA1 CALR PRF1 ABCB4 SMPD1 ABCD3 KCNN4 SEC23B ICOS NPM1 ITK BCR MEFV JAK2 BPGM IL10 STX11 SLC4A1 PTPRC SLC17A5 COG7 IL12A-AS1 THPO FAH PIK3C2A ARVCF CALR BACH2 ATP6V1B2 CDAN1 JAK2 PHKG2 TNFRSF13C ABCA1 ITCH MST1 SEC24C IDUA IL2RG COG6 CCND1 CD28 RUNX1 IDUA FUCA1 SPTB SCYL1 JMJD1C GNE COMT CA2 SPTB KRAS GPC3 SMPD1 TTC37 RHAG SPTA1 ATP7B SLC7A7 IGH GP1BA EPB42 GYPC HFE GPD1 GNS NEU1 FOS NCF1 PDGFRA TPP2 RNU4ATAC GBA IL1RN GBA HBB CAV1 PSAP SH2B3 PIGM TNFRSF13B MIF MMUT LIPA GP1BB SKIV2L VPS13A INPPL1 AP3B1 NOTCH2 NLRP3 GATA2 SNX10 ATM JAK2 RTEL1 NLRP12 HBB APOE SMPD1 SPTB CD19 CR2 JAK2 MPL AKR1D1 CYBB GPC4 DCLRE1C PSMB8 PSMB4 APOC2 DDRGK1 SGSH ARSB BTNL2 HSD3B7 ASAH1 CCBE1 CD27 PSAP LPIN2 HLA-DRB1 RREB1 PEPD DOLK TGFB1 GPI WRAP53 KLRC4 TET2 HLA-B FAS APOA1 ZAP70 ADAMTS3 PHKG2 CD81 EPB42 DKC1 OSTM1 PRKCD DGUOK ATP6AP1 GPC3 NLRP1 SOX10 NLRC4 TNFSF12 DYNC2LI1 ADA PTEN SLC30A10 FASLG PIK3R1 CTSK KLF1 ALG1 PIK3CA PPARG COX4I2 RMRP FGA ANK1 GATA1 G6PC3 PHYH ERCC6 HJV CCR1 LACC1 HBA1 MVK MS4A1 NBEAL2 BSCL2 FASLG LIG4 NFKB2 TBXAS1 APOE NEU1 CALR PLEKHM1 UROS HBA1 NOP10 LIPA GBA TNFRSF1B SUMF1 HBG1 NHP2 TBX1 THPO IDS MEFV HK1 ANK1 GBA RPGRIP1L DCDC2 G6PD LAT HLA-DRB1 ERBB3 PARN TET2 BSCL2 SLC29A3 GFI1B LCAT PEX7 GBA ICOS GATA1 TNFSF12 GLRX5 USB1 FAS LYST FMO3 SLC39A4 AGA GPR35 CTNS CYBC1 HPGD CASP10 RAG2 MYD88 CCDC47 IDUA DPM1 PKLR TNFRSF13B CLCN7 HAMP BTD SAMD9L CC2D2A MKS1 NPC1 CPOX RNASEH2A GLIS3 VPS45 BCL2 AKT1 CAVIN1 PTEN NOTCH1 JAK2 GBA TNFRSF1A IL7R TALDO1 HBB NAGLU COG4 ABL1 IDUA SLC4A1 SLC2A1 RAG1 CYP7B1 UMPS CASK CALR IL12A PSMB8 TNFRSF1B IL23R SNX10 DNASE1L3 IL6 CTLA4 CLCN7 PNP PPARG HGSNAT CR2 ADA AP3D1 UFD1 CAVIN1 FAT4 CC2D2A GBA TMEM67 CD19 TNFSF11 CYBB F5 TCIRG1 AKT1 GAA CYBA ATP8B1 RAG1 JAK2 PSMB9 NCF1 WDR35 TERC CAV1 CARD11 OCLN HBB MCM4 NLRC4 PIEZO1 FOXP3 IRF8 ERAP1 CLCN7 CTC1 LYST INPP5E HAVCR2 ABCG8 MPL CASR IGH KCNH1 CTLA4 DCLRE1C FAS ICOS DCDC2 CTLA4 XIAP IL7R LIPA SH2B3 BCL6 NOD2 VPS33A HBG2 CASP8 EPB41 RAG1 CFAP410 ALMS1 NCF2 TNFRSF13C GALE ABCB11 SLC4A1 SH2B3 ANK1 FAS NCF2 AKR1D1 IL2RA TLR4 ALDOA GPC4 STAT4 PRKCD DDRGK1 HFE SH2B3 SH2D1A CCND1 TET2 MVK ADA2 RHAG XIAP MPIG6B SCARB2 CHD7 LBR LPL ALAS2 HLA-DRB1 C15ORF41 FAH TCF4 HBA2 OTC CD40LG PEX2 UBAC2 TINF2 RAB27A TPI1 GATA1 GNPTAB C4A CD28 NBEAL2 RAG2 PTEN GLB1 AGPAT2 DGUOK NFKB1 GPIHBP1 NCF4 UROS PHKA2 TCIRG1 MEFV PKHD1 MAN2B1 ERCC8 GBA MVK GUSB PIK3CD APOA1 TBX1 TET2 TERT JAK2
B-cell lymphoma
Genes 17
IGH FAS CASP10 ADA FAS FASLG BCL10 PIK3R1 BIRC3 FOXP1 RASGRP1 CCND1 ATM PRKCD MALT1 NBN IGH
Multiple myeloma
Genes 3
LIG4 CCND1 GBA
Hepatocellular carcinoma
Genes 65
AHCY CTNNB1 CASP10 IGF2R JAG1 CASP8 HFE BMP2 HFE MLH1 PMS2 POU2AF1 HMBS FAH MSH6 SLC25A13 RASGRP1 EPCAM UROD AXIN1 TCF4 TP53 IL12A PRKCD SLC37A4 TGFBR2 SEMA4A JAK2 FAN1 FAS BMPR1A FAS KRAS FAH SPIB MSH2 HMBS MST1 MLH3 G6PC SPRTN SLC37A4 PIK3CA PDGFRL SERPINA1 TNFSF15 ATP7B IGF2 ABCB11 FASLG IL12RB1 SLC25A13 IRF5 RPS20 MET PIK3CA MMEL1 HFE H19 PMS1 F5 GPR35 APC TJP2 TNPO3
Bladder neoplasm
Genes 30
CTNNB1 BUB1 COL14A1 RNF43 HRAS AAGAB DLC1 AKT1 PIK3CA FLCN AKT1 FGFR3 NTHL1 PTEN HRAS NRAS EP300 SRC BUB1B APC AXIN2 KRAS ATP7A NTHL1 RB1 PTPRJ PIK3CA DCC TP53 FGFR3