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

NCT02873832 | Completed

• 1 other identifier: GIRODON 2014
• Study Type: observational
• Target: 37
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 .

  Level of protein expression using flow cytometry and western blot

  through study completion, an average of 1 year

Secondary Outcomes (1)

• Cell death after in vitro treatment with different HSP inhibitors

  through study completion, an average of 1 year

Study Arms (2)

MPS

Biological: Blood sample; Other: Flow cytometry; Other: western blot

Control

Biological: Blood sample; Other: Flow cytometry; Other: western blot

Interventions

Blood sample BIOLOGICAL

Control; MPS

Flow cytometry OTHER

Control; MPS

western blot OTHER

Control; MPS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Myeloproliferative Syndrom

You may qualify if:

• 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

You may not qualify if:

• Adults under guardianship

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

CHU Dijon Bourgogne

Dijon, 21079, France

Location

MeSH Terms

Interventions

Blood Specimen Collection; Flow Cytometry; Blotting, Western

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cell Separation; Cytological Techniques; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Electrophoresis; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques

Study Design

• Study Type: observational
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 22, 2016
• Study Start: January 1, 2015
• Primary Completion: April 1, 2016
• Last Updated: August 22, 2016

Record last verified: 2016-07

Locations

FR (1)