Author/Authors :
Levine، نويسنده , , Ross L. and Wadleigh، نويسنده , , Martha and Cools، نويسنده , , Jan and Ebert، نويسنده , , Benjamin L. and Wernig، نويسنده , , Gerlinde and Huntly، نويسنده , , Brian J.P. and Boggon، نويسنده , , Titus J. and Wlodarska، نويسنده , , Iwona and Clark، نويسنده , , Jennifer J. and Moore، نويسنده , , Sandra and Adelsperger، نويسنده , , Jennifer and Koo، نويسنده , , Sumin and Lee، نويسنده , , Jeffrey C. and Gabriel، نويسنده , , Stacey and Mercher، نويسنده , , Thomas and D’Andrea، نويسنده , , Alan and Fr?hling، نويسنده , , Stefan and D?hner، نويسنده , , Konstanze and Marynen، نويسنده , , Peter and Vandenberghe، نويسنده , , Peter and Mesa، نويسنده , , Ruben A. and Tefferi، نويسنده , , Ayalew and Griffin، نويسنده , , James D. and Eck، نويسنده , , Michael J. and Sellers، نويسنده , , William R. and Meyerson، نويسنده , , Matthew and Golub، نويسنده , , Todd R. and Lee، نويسنده , , Stephanie J. and Gilliland، نويسنده , , D. Gary، نويسنده ,
Abstract :
Summary
themia 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.
