title: JAK2 V617F genotype is a strong determinant of blast transformation in primary myelofibrosis.
abstract: OBJECTIVE
  The influence of JAK2 V617F mutation on blast transformation (BT) and overall survival (OS) in primary myelofibrosis (PMF) is controversial. In a large cohort of patients we applied competing risks analysis for studying the influence of JAK2V617F mutation on BT in PMF.
  
  
  METHODS
  In 462 PMF-fibrotic type patients (bone marrow [BM] fibrosis grade >0) we computed the incidence of BT and death in the framework of Cox regression analysis and of Fine and Gray competing risks analysis for BT.
  
  
  RESULTS
  At the Cox regression analysis, having either a wild-type (wt) or a homozygous JAK2V617F genotype were factors for BT (HR, 1.98 and 2.04, respectively, with respect to the heterozygous genotype), but not for OS. At the competing risks regression analysis, the risk for BT in wt and homozygous V617F patients increased with respect to Cox analysis, giving a sHR of 2.17 and 2.12, respectively. Correcting the results for the variables that could have influence on BT, JAK2V617F wt and homozygous genotypes remained independently associated with BT. In a validation cohort of 133 independent cases with PMF-prefibrotic type (BM fibrosis grade = 0), the BT predictive model including JAK2V617F genotype and older age retained high discriminant capacity (C statistics, 0.70; 95% CI, 0.47 to 0.92).
  
  
  CONCLUSIONS
  The accumulation of mutated alleles in the JAK2V617F clone or the selective acquisition of a proliferative advantage in the wt clone are two relevant routes to BT in PMF. The influence of these results on treatment decisions with anti-JAK2 agents should be tested.
authors.affiliation: Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy. barosig@smatteo.pv.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
authors.forename: Valentina
authors.initials: V
authors.lastname: Poletto
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.forename: Rita
authors.initials: R
authors.lastname: Campanelli
authors.forename: Laura
authors.initials: L
authors.lastname: Villani
authors.forename: Elisa
authors.initials: E
authors.lastname: Bonetti
authors.forename: Gianluca
authors.initials: G
authors.lastname: Viarengo
authors.forename: Paolo
authors.initials: P
authors.lastname: Catarsi
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001854:Bone Marrow Cells; D002648:Child; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000401:mortality*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2
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