title: The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates.
abstract: An association between an activating JAK2 mutation (JAK2(V617F)) and BCR/ABL-negative myeloproliferative disorders was recently reported in multiple simultaneous publications. In the current study, mutation analysis for JAK2(V617F) was performed in peripheral blood mononuclear cells (PBMC) from 157 patients with myelofibrosis with myeloid metaplasia (MMM) including 117 with agnogenic (AMM), 22 with postpolycythaemic (PPMM), and 18 with post-thrombocythaemic (PTMM) myeloid metaplasia. The detection rate for JAK2(V617F) was significantly higher in PPMM (91%; homozygous in 18%) compared with either AMM (45.3%; homozygous in 2.6%) or PTMM (38.9%; homozygous in 11.1%). Concomitant analysis in granulocytes (n=57) and CD34(+) cells (n=25) disclosed a higher incidence of homozygous JAK2(V617F) mutation but the overall mutation rate was similar to that obtained from PBMC. JAK2(V617F) was not detected in DNA derived from T cells (n=19). In AMM, the presence of JAK2(V617F) was associated with an older age at diagnosis and a history of thrombosis or pruritus. Multivariate analysis identified only age and the Dupriez prognostic score as independent prognostic factors; JAK2(V617F) had no prognostic significance. In conclusion, JAK2(V617F) is a myeloid lineage-specific event, its incidence in MMM is significantly higher with an antecedent history of polycythaemia vera (PV), and its presence in AMM does not affect prognosis but is associated with PV-characteristic clinical features.
authors.affiliation: Mayo Clinic and Mayo Clinic College of Medicine, Rochester, MN 55905, USA. trfferi.ayalew@mayo.edu
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.forename: Susan M
authors.initials: SM
authors.lastname: Schwager
authors.forename: David P
authors.initials: DP
authors.lastname: Steensma
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.forename: Chin-Yang
authors.initials: CY
authors.lastname: Li
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.forename: D
authors.initials: D
authors.lastname: Gary Gilliland
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D053614:Janus Kinase 2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011087:Polycythemia Vera / Q000201:enzymology / Q000235:genetics; D055728:Primary Myelofibrosis / Q000201:enzymology / Q000235:genetics*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013922:Thrombocytosis / Q000201:enzymology / Q000235:genetics
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2