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Report for Clinical Trial NCT02873832

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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
MeSH:Myeloproliferative Disorders Syndrome
HPO:Myeloproliferative disorder

3 Interventions

Name: Blood sample

Type: Biological
Group Labels: 2

Control MPS

Name: Flow cytometry

Type: Other
Group Labels: 2

Control MPS

Name: western blot

Type: Other
Group Labels: 2

Control MPS


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

Time Perspective: Retrospective


There is one SNP

SNPs


1 V617F

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



HPO Nodes


HPO: