Characterization of Clonal Hematopoiesis of Indeterminate Potential as a Genetic Risk Factor in Patients Diagnosed with BCR::ABL1-negative Myeloproliferative Neoplasms
Description: BCR::ABL1-negative Myeloproliferative Neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF), are chronic clonal hematologic disorders characterized by increased proliferation of mature myeloid cells, often driven by mutations such as JAK2V617F, in the absence of the BCR::ABL1 fusion gene. Clonal Hematopoiesis (CH) arises from the expansion of hematopoietic stem cells (HSCs) harboring somatic mutations, which precede overt malignancy and are associated with aging and cardiovascular complications. A specific subset, Clonal Hematopoiesis of Indeterminate Potential (CHIP), defined by mutations in genes such as DNMT3A, TET2, and ASXL1 (DTA mutations), has been identified as a significant risk factor for thrombotic events.Thrombosis is a major cause of morbidity and mortality in MPN patients, particularly in arterial territories, including stroke. Current risk stratification models consider factors such as age >60, previous thrombosis, cardiovascular risk factors, and JAK2V617F mutation status; however, up to 20% of MPN patients experience thrombosis at diagnosis, underscoring the need for earlier predictive markers. Data from our institution show that approximately one-third of MPN patients develop thrombotic events during follow-up. In this context, CHIP emerges as a promising biomarker for improved risk assessment and clinical management of thrombosis in MPNs. (AU)
Funding type: grant
Funder scheme: Auxílio à Pesquisa - Regular
Start date: 2025-10-01
End date: 2026-09-30
Investigator: Lorena Lôbo de Figueiredo Pontes
Institution: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Hemocentro de Ribeirão Preto
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 25/13957-9
OpenAlex ID: G1319082237