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.
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.forename: Jan
authors.initials: J
authors.lastname: Cools
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Ebert
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Wernig
authors.forename: Brian J P
authors.initials: BJ
authors.lastname: Huntly
authors.forename: Titus J
authors.initials: TJ
authors.lastname: Boggon
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Clark
authors.forename: Sandra
authors.initials: S
authors.lastname: Moore
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adelsperger
authors.forename: Sumin
authors.initials: S
authors.lastname: Koo
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lee
authors.forename: Stacey
authors.initials: S
authors.lastname: Gabriel
authors.forename: Thomas
authors.initials: T
authors.lastname: Mercher
authors.forename: Alan
authors.initials: A
authors.lastname: D'Andrea
authors.forename: Stefan
authors.initials: S
authors.lastname: Fröhling
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.forename: James D
authors.initials: JD
authors.lastname: Griffin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eck
authors.forename: William R
authors.initials: WR
authors.lastname: Sellers
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005838:Genotype; D006098:Granulocytes / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics; D008958:Models, Molecular; D009061:Mouth Mucosa / Q000378:metabolism; D020125:Mutation, Missense / Q000235:genetics*; D010766:Phosphorylation; D011087:Polycythemia Vera / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000150:complications / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics*; D014162:Transfection
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2