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Exploring the Mechanisms of Resistance of Stem Cells Myeloproliferative Opposite of Tyrosine Kinase Inhibitors in 3d Model Niche Endosteal

NCT02766153 · Status: TERMINATED · Type: OBSERVATIONAL · Enrollment: 200

Last updated 2024-02-05

No results posted yet for this study

Summary

Myeloproliferative disorders (MPD) include chronic myeloid leukemia (CML) (Ph +) and essential thrombocythemia (ET), the polycythemia vera (PV), myelofibrosis (MF) called SMP Ph. CML is the ultimate model of carcinogenesis. SMP is a characterized by a malignant monoclonal proliferation of a pluripotent hematopoietic progenitor determined by the presence of a balanced translocation between chromosomes 9 and 22 (Ph chromosome) which leads to major changes of a large number of cell functions. Investigators now believe that within the bone marrow exist two types of "hematopoietic niches' niche osteoblastic / endosteal and vascular niche, controlling the maintenance and differentiation of hematopoietic stem cell pool. The endosteal niche, is a hypoxic region near the endosteal trabecular, which provides protection to deeply dormant stem cells. Data from the literature suggest that in the SMP, especially CML, the interaction of malignant stem cells with the microenvironment niche Endosteal could favor their survival and resistance to treatment. The therapeutic management of CML was upset by the use of tyrosine kinase inhibitors (TKIs). However, despite these advances, even in situations of undetectable residual disease, it has been observed relapses of the disease stopped TKI leaving suggest that there is a resistance of leukemic stem cell to TKI.

Work in the group Bipoa "Bio Engineering and Pathophysiology Osteo-Articular" helped develop a 3D model of ex vivo bone formation, which can mimic the endosteal niche. the goal is to apply this model to the SMP of hematopoiesis by referring to normal hematopoiesis. it will be tested the hypothesis that the endosteal ex vivo recess of the 3D modeling allows to highlight a special interaction can promote the persistence of the leukemia stem cell despite the use of effective therapies.

Conditions

  • Myeloproliferative Disorders

Sponsors & Collaborators

  • Centre National de la Recherche Scientifique, France

    collaborator OTHER

  • Centre Hospitalier Universitaire de Nice

    lead OTHER

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2016-05-31
Primary Completion
2020-04-30
Completion
2020-12-31

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02766153 on ClinicalTrials.gov