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Functional Characterization of Thrombopoietin/cMPL Receptor Mutations in Myeloproliferative Neoplasia

NCT06246006 · Status: ACTIVE_NOT_RECRUITING · Type: OBSERVATIONAL · Enrollment: 30

Last updated 2024-02-07

No results posted yet for this study

Summary

The MPL gene is implicated in two groups of hematological pathologies: congenital amegakaryocytic thrombocytopenia (CAMT) and Phi negative myeloproliferative neoplasia (MPN). Fifty germline mutations have been identified in CAMT, yet only a dozen activating mutations have been described in MPN. Most are somatic, distributed mainly in the transmembrane (TM) and juxtamembrane (JM) domains. However, a few rare germline mutations located in the extracellular domain (ECD) have also been reported: K39N, R102P and P106L.

Next generation sequencing technology has been used to study the complete MPL gene, identifying numerous variants, most of unknown significance. The study investigators have a series comprising 41 variants of unknown significance, whose allelic frequencies suggest a germline origin for 80% of them. Their distribution within the MPL gene is similar to that of inactivating mutations, except that they were discovered in the context of suspected myeloproliferative disease. Characterizing the activity of these variants would confirm the diagnosis of MPN, opening the door to specific treatment (cytoreductive, JAK2 inhibitor or interferon). It also has an important prognostic value, particularly in the case of MPN, for which life expectancy varies from 5 to 7 years, with terminal progression to acute myeloid leukemia (AML in 15 to 20% of cases) or bone marrow failure.

Using a battery of functional assays, this study aims to characterize these variants.

Conditions

  • Myeloproliferative Disorder

Interventions

OTHER

Gene sequencing

Next generation sequencing of candidate genes (JAK2, cMPL, CALR, ASXL1 and NF-E2)

Sponsors & Collaborators

  • Centre Hospitalier Universitaire de Nīmes

    lead OTHER

Principal Investigators

  • Serge Carillo · CHU de Nimes

Eligibility

Min Age
18 Years
Max Age
99 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-10-01
Primary Completion
2025-04-30
Completion
2025-04-30

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 NCT06246006 on ClinicalTrials.gov