A germline JAK2 SNP is associated with predisposition to the development of JAK2V617F-positive myeloproliferative neoplasms

摘要: Polycythemia vera, essential thrombocythemia and primary myelofibrosis are myeloproliferative neoplasms (MPN) characterized by multilineage clonal hematopoiesis. Given that the identical somatic activating mutation in JAK2 tyrosine kinase gene (JAK2(V617F)) is observed most individuals with polycythemia myelofibrosis, there likely additional genetic events contribute to pathogenesis of these phenotypically distinct disorders. Moreover, family members MPN at higher risk for development MPN, consistent existence predisposition loci. We hypothesized germline variation contributes phenotypic pleiotropy. Genome-wide analysis identified an allele locus (rs10974944) predisposes JAK2(V617F)-positive as well three previously unknown modifier found JAK2(V617F) preferentially acquired cis allele. These data suggest important contributor phenotype predisposition.