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NCT Number: NCT06923670

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

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.

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Key information

Conditions

Polycythemia Vera Blood Coagulation Disorders Blood Platelet Disorders Bone Marrow Diseases Bone Marrow Neoplasms Essential Thrombocythaemia Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Hemorrhagic Disorders Myelofibrosis Myeloproliferative Disorders Neoplasms Neoplasms by Site Primary Myelofibrosis Thrombocythemia, Essential Thrombocytosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

NGS testing

Diagnostic Test

The investigators will test in NGS the presence of mutations 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

NGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

Diagnostic Test

The investigators will evaluate the presence of mutations 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

Primary outcomes

  1. Comparison between clinical characteristis in patients with and without family history:

    Time frame: 30 months

    Complete blood count test Presence of splenomegaly Presence of Fibrosis at bone marrow biopsy

  2. Comparison between biological characteristis in patients with and without family history:

    Time frame: 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 outcomes

  1. Prevalence of germline mutations in MPN patients

    Time frame: 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

  2. Distribution of hematologic malignancies in the group with familial hystory

    Time frame: 36

    Prevalence of hematological malignancies in the group with familial history

Study contacts

Contact information is provided by the study sponsor or research team.

Denise Soldati, Data Manager

CONTACT

[email protected]

390630154206

Patrizia chiusolo, MD

CONTACT

[email protected]

393355267999

Sponsors and collaborators

Lead sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Other

Registry information

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Apr 11, 2025
Registry last updated
May 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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