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

NCT ID: NCT02873832

Last Updated: 2016-08-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 37 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-01-31

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.

Conditions

Myeloproliferative Syndrome

Study Design

• Study Time Perspective: RETROSPECTIVE

Study Groups

MPS

Blood sample

Intervention Type: BIOLOGICAL

Flow cytometry

Intervention Type: OTHER

western blot

Intervention Type: OTHER

Control

Blood sample

Intervention Type: BIOLOGICAL

Flow cytometry

Intervention Type: OTHER

western blot

Intervention Type: OTHER

Interventions

Blood sample

Intervention Type: BIOLOGICAL

Flow cytometry

Intervention Type: OTHER

western blot

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire Dijon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU Dijon Bourgogne

Dijon, , France

Countries

France

Other Identifiers

GIRODON 2014

Identifier Type: -

Identifier Source: org_study_id