title: JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis.
abstract: Few investigators have evaluated the usefulness of the JAK2 V617F mutation for explaining the phenotypic variations and for predicting the risk of major clinical events in primary myelofibrosis (PMF). In a transversal survey we assayed by allele-specific polymerase chain reaction (PCR) the JAK2 V617F mutational status in 304 patients with PMF. Multiple DNA samples were collected prospectively from 64 patients, and a highly sensitive quantitative PCR was used as a confirmatory test. In a longitudinal prospective study we determined the progression rate to clinically relevant outcomes in 174 patients who had JAK2 mutation determined at diagnosis. JAK2 V617F was identified in 63.4% of patients. None of the V617F-negative patients who were sequentially genotyped progressed to become V617F positive, whereas progression rate from heterozygous to homozygous mutation was 10 per 100 patient-years. JAK2 V617F mutation contributed to hemoglobin, aquagenic pruritus, and platelet count variability, whereas homozygous mutation was independently associated with higher white blood cell count, larger spleen size, and greater need for cytoreductive therapies. Adjusting for conventional risk factors, V617F mutation independently predicted the evolution toward large splenomegaly, need of splenectomy, and leukemic transformation. We conclude that JAK2 V617F genotype should be considered in any future risk stratification of patients with PMF.
authors: Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo Foundation, Pavia, Italy. barosig@smatteo.pv.it
authors: Giovanni
authors: G
authors: Barosi
authors: Gaetano
authors: G
authors: Bergamaschi
authors: Monia
authors: M
authors: Marchetti
authors: Alessandro M
authors: AM
authors: Vannucchi
authors: Paola
authors: P
authors: Guglielmelli
authors: Elisabetta
authors: E
authors: Antonioli
authors: Margherita
authors: M
authors: Massa
authors: Vittorio
authors: V
authors: Rosti
authors: Rita
authors: R
authors: Campanelli
authors: Laura
authors: L
authors: Villani
authors: Gianluca
authors: G
authors: Viarengo
authors: Elisabetta
authors: E
authors: Gattoni
authors: Giancarla
authors: G
authors: Gerli
authors: Giorgina
authors: G
authors: Specchia
authors: Carmine
authors: C
authors: Tinelli
authors: Alessandro
authors: A
authors: Rambaldi
authors: Tiziano
authors: T
authors: Barbui
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D007938:Leukemia / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D055728:Primary Myelofibrosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D013163:Splenomegaly / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D013997:Time Factors
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2