title: JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia.
abstract: An activating 1849G>T mutation of JAK2 (Janus kinase 2) tyrosine kinase was recently described in chronic myeloproliferative disorders (MPDs). Its role in other hematologic neoplasms is unclear. We developed a quantitative pyrosequencing assay and analyzed 374 samples of hematologic neoplasms. The mutation was frequent in polycythemia vera (PV) (86%) and myelofibrosis (95%) but less prevalent in acute myeloid leukemia (AML) with an antecedent PV or myelofibrosis (5 [36%] of 14 patients). JAK2 mutation was also detected in 3 (19%) of 16 patients with Philadelphia-chromosome (Ph)-negative chronic myelogenous leukemia (CML), 2 (18%) of 11 patients with megakaryocytic AML, 7 (13%) of 52 patients with chronic myelomonocytic leukemia, and 1 (1%) of 68 patients with myelodysplastic syndromes. No mutation was found in Ph(+)CML (99 patients), AML M0-M6 (28 patients), or acute lymphoblastic leukemia (20 patients). We conclude that the JAK2 1849G>T mutation is common in Ph(-) MPD but not critical for transformation to the acute phase of these diseases and that it is generally rare in aggressive leukemias.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA. jjelinek@mdanderson.org
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Jelinek
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.forename: Vazganush
authors.initials: V
authors.lastname: Gharibyan
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Elihu
authors.initials: E
authors.lastname: Estey
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Jean-Pierre J
authors.initials: JP
authors.lastname: Issa
mesh_terms: D006801:Humans; D053614:Janus Kinase 2; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics*; D011087:Polycythemia Vera / Q000235:genetics / Q000378:metabolism; D055728:Primary Myelofibrosis / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2