@article{6bc17695006b461aa60f2519c42585c4,
title = "Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis",
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.",
author = "Levine, {Ross L.} and Martha Wadleigh and Jan Cools and Ebert, {Benjamin L.} and Gerlinde Wernig and Huntly, {Brian J.P.} and Boggon, {Titus J.} and Iwona Wlodarska and Clark, {Jennifer J.} and Sandra Moore and Jennifer Adelsperger and Sumin Koo and Lee, {Jeffrey C.} and Stacey Gabriel and Thomas Mercher and Alan D'Andrea and Stefan Fr{\"o}hling and Konstanze D{\"o}hner and Peter Marynen and Peter Vandenberghe and Mesa, {Ruben A.} and Ayalew Tefferi and Griffin, {James D.} and Eck, {Michael J.} and Sellers, {William R.} and Matthew Meyerson and Golub, {Todd R.} and Lee, {Stephanie J.} and Gilliland, {D. Gary}",
note = "Funding Information: Supported in part by National Institute of Health grants DK50654 and CA66996 to D.G.G., the Belgian Federation against Cancer to J.C., and by the Leukemia and Lymphoma Society. D.G.G. is a Doris Duke Foundation Distinguished Clinical Scientist; D.G.G. and T.R.G are Investigators of the Howard Hughes Medical Institute. M.W. is a recipient of an American Society of Clinical Oncology Young Investigator Award, J.C. is a postdoctoral researcher of the “FWO-Vlaanderen,” B.J.P.H is a senior clinical fellow of the LRF (UK), T.J.B. is a recipient of an American Society of Hematology Basic Research Scholar Award, and S.F. is supported by grant FR 2113/1-1 from the Deutsche Forschungsgemeinschaft. We thank the myeloproliferative disease patients who participated in this study, and Joyce Niblack, J.D., for support and access to the mpdinfo.org website. We thank Radek Skoda and Tony Green for sharing data prior to publication. We are indebted to Sarah Cohen, Allison Coburn, Rachel Okabe, Elizabeth McDowell, Dana Cullen, Gulnar Pothiawala, Nicole Mentens, and Claudia Tenen for assistance with sample processing, to Tarrah Kirkpatrick and Arnold Gonzales for assistance with the MPD study, to Liuda Ziaugra for assistance with Sequenom genotyping, and to Alexis Bywater for technical and administrative assistance. PCR and sequencing were performed through a contractual arrangement with Agencourt Bioscience Corporation. ",
year = "2005",
month = apr,
doi = "10.1016/j.ccr.2005.03.023",
language = "English (US)",
volume = "7",
pages = "387--397",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}