Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis |
| |
Authors: | Levine Ross L Wadleigh Martha Cools Jan Ebert Benjamin L Wernig Gerlinde Huntly Brian J P Boggon Titus J Wlodarska Iwona Clark Jennifer J Moore Sandra Adelsperger Jennifer Koo Sumin Lee Jeffrey C Gabriel Stacey Mercher Thomas D'Andrea Alan Fröhling Stefan Döhner Konstanze Marynen Peter Vandenberghe Peter Mesa Ruben A Tefferi Ayalew Griffin James D Eck Michael J Sellers William R Meyerson Matthew Golub Todd R Lee Stephanie J Gilliland D Gary |
| |
Affiliation: | Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|