Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis

Ross L. Levine, Martha Wadleigh, Jan Cools, Benjamin L. Ebert, Gerlinde Wernig, Brian J.P. Huntly, Titus J. Boggon, Iwona Wlodarska, Jennifer J. Clark, Sandra Moore, Jennifer Adelsperger, Sumin Koo, Jeffrey C. Lee, Stacey Gabriel, Thomas Mercher, Alan D'Andrea, Stefan Fröhling, Konstanze Döhner, Peter Marynen, Peter VandenbergheRuben A. Mesa, Ayalew Tefferi, James D. Griffin, Michael J. Eck, William R. Sellers, Matthew Meyerson, Todd R. Golub, Stephanie J. Lee, D. Gary Gilliland

Research output: Contribution to journalArticlepeer-review

2182 Scopus citations

Abstract

Polycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are clonal disorders arising from hematopoietic progenitors. An internet-based protocol was used to collect clinical information and biological specimens from patients with these diseases. High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations. Molecular and cytogenetic analyses demonstrated that homozygous mutations were due to duplication of the mutant allele. JAK2V617F was also identified in granulocyte DNA samples from 37 of 115 ET and 16 of 46 MMM patients, but was not observed in 269 normal individuals. In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase.

Original languageEnglish (US)
Pages (from-to)387-397
Number of pages11
JournalCancer Cell
Volume7
Issue number4
DOIs
StatePublished - Apr 2005

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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