title: Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations.
abstract: Although approximately 95% of patients with polycythemia vera (PV) harbor the V617F mutation in JAK2 exon 14, several mutations in exon 12 have been described in the remaining patients. We conducted a European collaborative study to define the molecular and clinical features of patients harboring these mutations. Overall, 106 PVs were recruited and 17 different mutations identified. Irrespective of the mutation, two-thirds of patients had isolated erythrocytosis, whereas the remaining subjects had erythrocytosis plus leukocytosis and/or thrombocytosis. Compared with JAK2 (V617F)-positive PV patients, those with exon 12 mutations had significantly higher hemoglobin level and lower platelet and leukocyte counts at diagnosis but similar incidences of thrombosis, myelofibrosis, leukemia, and death. In a multivariable analysis, age more than 60 years and prior thrombosis predicted thrombosis. These findings suggest that, despite the phenotypical difference, the outcome of JAK2 exon 12 mutations-positive PV is similar to that of JAK2 (V617F)-positive PV.
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.forename: Chiara
authors.initials: C
authors.lastname: Elena
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Green
authors.forename: François
authors.initials: F
authors.lastname: Girodon
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: McMullin
authors.forename: Marco
authors.initials: M
authors.lastname: Ruggeri
authors.forename: Carles
authors.initials: C
authors.lastname: Besses
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehmann
authors.forename: Christina A
authors.initials: CA
authors.lastname: Ortmann
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietra
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D053614:Janus Kinase 2 / Q000235:genetics*; D007964:Leukocytosis / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011086:Polycythemia / Q000209:etiology / Q000235:genetics; D011087:Polycythemia Vera / Q000150:complications / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D013922:Thrombocytosis / Q000209:etiology / Q000235:genetics; D055815:Young Adult
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2