A Germline JAK2 SNP is Associated with Predisposition to the Development of JAK2(V617F)-positive Myeloproliferative Neoplasms

Overview

Journal Nat Genet

Specialty Genetics

Date 2009 Mar 17

PMID 19287384

Citations 160

Authors

Outi Kilpivaara

Semanti Mukherjee

Alison M Schram

Martha Wadleigh

Ann Mullally

Benjamin L Ebert

Adam Bass

Sachie Marubayashi

Adriana Heguy

Guillermo Garcia-Manero

Hagop Kantarjian

Kenneth Offit

Richard M Stone

D Gary Gilliland

Robert J Klein

Ross L Levine

Affiliations

Soon will be listed here.

Abstract

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

Citing Articles

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