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Cancer Cell DOI:10.1016/j.ccr.2005.03.023

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

Publication TypeJournal Article
Year of Publication2005
AuthorsLevine, RL, Wadleigh, M, Cools, J, Ebert, BL, Wernig, G, Huntly, BJP, Boggon, TJ, Wlodarska, I, Clark, JJ, Moore, S, Adelsperger, J, Koo, S, Lee, JC, Gabriel, S, Mercher, T, D'Andrea, A, Fröhling, S, Döhner, K, Marynen, P, Vandenberghe, P, Mesa, RA, Tefferi, A, Griffin, JD, Eck, MJ, Sellers, WR, Meyerson, M, Golub, TR, Lee, SJ, D Gilliland, G
JournalCancer Cell
Date Published2005 Apr
KeywordsAdult, Aged, Aged, 80 and over, Cell Line, Tumor, Enzyme Activation, Female, Genotype, Granulocytes, Heterozygote, Homozygote, Humans, Janus Kinase 2, Male, Middle Aged, Mitosis, Models, Molecular, Mouth Mucosa, Mutation, Missense, Phosphorylation, Polycythemia Vera, Primary Myelofibrosis, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Recombination, Genetic, Thrombocythemia, Essential, Transfection

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.


Alternate JournalCancer Cell
PubMed ID15837627
Grant ListT32 CA009172 / CA / NCI NIH HHS / United States
CA66996 / CA / NCI NIH HHS / United States
DK50654 / DK / NIDDK NIH HHS / United States