Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS)

Completed

• Conditions: Myeloproliferative Syndrome
• Interventions: Biological: Blood sample; Other: Flow cytometry; Other: western blot

• Registration Number: NCT02873832
• Lead Sponsor: Centre Hospitalier Universitaire Dijon

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01
• Primary Completion: 2016-04
• Status Verified: 2016-07
• Study First Submitted: 2016-08-04
• Study First Submitted QC: 2016-08-16
• Last Update Submitted: 2016-08-16
• Study First Posted: 2016-08-22
• Last Update Posted: 2016-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

MPS Patients:

• Patients with MPS
• Patients who have been informed and not objected to the tests
• Patients over 18 years old
• Patients whose samples have been preserved at the CRB in the "Haemopathies" collection

Control patients:

• Patients over 18 years old
• Pregnant patients
• Patients who have been informed and not objected to the collection of their cord blood after the delivery

Exclusion Criteria

• Adults under guardianship

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control	Blood sample	-
Control	Flow cytometry	-
MPS	western blot	-
MPS	Blood sample	-
MPS	Flow cytometry	-
Control	western blot	-

Primary Outcome Measures

Name	Time	Method
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 .	through study completion, an average of 1 year	Level of protein expression using flow cytometry and western blot

Secondary Outcome Measures

Name	Time	Method
Cell death after in vitro treatment with different HSP inhibitors	through study completion, an average of 1 year

Trial Locations

Locations (1)

CHU Dijon Bourgogne; 🇫🇷 Dijon, France