Essential Thrombocythaemia, Myelofibrosis, Polycythemia Vera
Conditions
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.
Interventions
DIAGNOSTIC_TESTNGS testing
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
DIAGNOSTIC_TESTNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
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
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Distribution of hematologic malignancies in the group with familial hystory | 36 | Prevalence of hematological malignancies in the group with familial history |
Contacts
Primary ContactPatrizia chiusolo, MD
Backup ContactDenise Soldati, Data Manager
Outcome results
None listed