Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

Not Applicable

Not yet recruiting

• Conditions: Polycythemia Vera; Essential Thrombocythaemia; Myelofibrosis

• Registration Number: NCT06923670
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary

Philadelphia-negative myeloproliferative neoplasms (MPNs) occur sporadically and are due to somatic mutations in the JAK2 (Janus kinase 2), CALR (calreticulin) and MPL (thrombopoietin receptor) genes. However, data from epidemiological and family studies clearly highlight a heritable component that influences the risk of developing MPN and potentially contributes to the observed phenotypic pleiotropy. Genome-wide association studies in MPN familial clusters have identified a number of germline genetic variants associated with an increased risk of developing MPN. The strongest association discovered so far is the presence of the JAK2 46/1 haplotype and, subsequently, several studies have found additional variants in other genes, particularly in the TERT gene.

The aim of the study would be to investigate the presence of germline mutations in MPN patients selected on the basis of a family history of myeloid neoplasms through the analysis of both already recognized genes and other potentially implicated ones.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-26
• Study First Submitted QC: 2025-04-04
• Study First Posted: 2025-04-11
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-15
• Study Start: 2025-05-21
• Primary Completion: 2028-05-01
• Study Completion: 2028-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 496

Inclusion Criteria

*Patients >18 years

• Diagnosis of MPN (Essential Thrombocythemia, Polycythemia Vera, Myelofibrosis) confirmed according to ICC 2022 criteria

• Familiarity for myeloid neoplasia: at least one first or second degree relative affected by myeloid neoplasia (probands) OR presence of matching criteria with a proband (controls). Each center will be able to contribute with its own available patients/relatives, providing the clinical-laboratory data required by the study.

  • Signing of informed consent according to ICH/EU/GCP and local national laws (if applicable)

Exclusion Criteria

• Patients <18 years Patients with other hematological diagnoses; • Lack of informed consen

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Comparison between clinical characteristis in patients with and without family history:	30 months	Complete blood count test Presence of splenomegaly Presence of Fibrosis at bone marrow biopsy
Comparison between biological characteristis in patients with and without family history:	30 months	Presence of driver mutations: JAK2 V617F Calreticulin mutations MPL mutations; Presence of detrimental mutations in the following genes: ASXL1, ZSFR2, IDH1, IDH2, EZH2, TP53

Secondary Outcome Measures

Name	Time	Method
Distribution of hematologic malignancies in the group with familial hystory	36	Prevalence of hematological malignancies in the group with familial history
Prevalence of germline mutations in MPN patients	36 months	Prevalence of germline mutations in MPN patients with familial hystory in the following genes: ABRAXAS1, ACD, ANKRD26, APC, ATG2B, ATM, BARD1, BMPR1A, BRCA1/2, BRIP1, CDH1, CDKN2A, CEBPA, CHECK2, CSF3R, DDX41, EPCAM, ERCC6L2, ETV6, FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCL, GATA2, GSKIP, MBD4, MECOM, MEN1, MLH1, MLH3, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NF2, PALB2, PIK3CA, POLD1, POLE, PMS2, PMS2CL, PTEN, PTPN11, RAD50, RAD51C, RAD51D, RET, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SRP72, STK11, TERC, TERT, TP53, TSC1, TSC2, VHL, WAS, XRCC2