Functional Characterization of Thrombopoietin/cMPL Receptor Mutations in Myeloproliferative Neoplasia

NCT ID: NCT06246006

Last Updated: 2024-02-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2025-04-30

Brief 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

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Study Groups

Patients with suspected MPN

Gene sequencing

Intervention Type: OTHER

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

Interventions

Gene sequencing

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patient with suspected MPN

Exclusion Criteria

• Patient with variant of cMPL already described in the literature.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Serge Carillo

Role: PRINCIPAL_INVESTIGATOR

CHU de Nimes

Locations

CHU de Nîmes

Nîmes, , France

Countries

France

Other Identifiers

NIMAO/2023-1/SC01

Identifier Type: -

Identifier Source: org_study_id