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

Cancer Cell
Authors
Keywords
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.

Year of Publication
2005
Journal
Cancer Cell
Volume
7
Issue
4
Pages
387-97
Date Published
2005 Apr
ISSN
1535-6108
URL
DOI
10.1016/j.ccr.2005.03.023
PubMed ID
15837627
Links
Grant list
T32 CA009172 / CA / NCI NIH HHS / United States
CA66996 / CA / NCI NIH HHS / United States
DK50654 / DK / NIDDK NIH HHS / United States