title: [Prognostic value of JAK2, MPL and CALR mutations in Chinese patients with primary myelofibrosis].
abstract: OBJECTIVE
  To evaluate the prognostic value of JAK2, MPL and CALR mutations in Chinese patients with primary myelofibrosis (PMF).
  
  
  METHODS
  Four hundred and two Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, the Log-rank test, the likelihood ratio test and the Cox proportional hazards regression model were used to evaluate the prognostic scoring system.
  
  
  RESULTS
  This cohort of patients included 209 males and 193 females with a median age of 55 years (range: 15- 89). JAK2V617F mutations were detected in 189 subjects (47.0% ), MPLW515 mutations in 13 (3.2%) and CALR mutations in 81 (20.1%) [There were 30 (37.0%) type-1, 48 (59.3%) type-2 and 3 (3.7%) less common CALR mutations], respectively. 119 subjects (29.6%) had no detectable mutation in JAK2, MPL or CALR. Univariate analysis indicated that patients with CALR type-2 mutations or no detectable mutations had inferior survival compared to those with JAK2, MPL or CALR type- 1 or other less common CALR mutations (the median survival was 74vs 168 months, respectively [HR 2.990 (95% CI 1.935-4.619),P<0.001]. Therefore, patients were categorized into the high-risk with CALR type- 2 mutations or no detectable driver mutations and the low- risk without aforementioned mutations status. The DIPSS-Chinese molecular prognostic model was proposed by adopting mutation categories and DIPSS-Chinese risk group. The median survival of patients classified in low risk (132 subjects, 32.8% ), intermediate- 1 risk (143 subjects, 35.6%), intermediate- 2 risk (106 subjects, 26.4%) and high risk (21 subjects, 5.2%) were not reached, 156 (95% CI 117- 194), 60 (95% CI 28- 91) and 22 (95% CI 10- 33) months, respectively, and there was a statistically significant difference in overall survival among the four risk groups (P<0.001). There was significantly higher predictive power for survival according to the DIPSS-Chinese molecular prognostic model compared with the DIPSS-Chinese model (P=0.005, -2 log-likelihood ratios of 855.6 and 869.7, respectively).
  
  
  CONCLUSIONS
  The impact of the CALR type- 2 mutations or no detectable driver mutation on survival was independent of current prognostic scoring systems. The DIPSS- Chinese molecular prognostic model based on the molecular features of Chinese patients was proposed and worked well for prognostic indication.
authors.affiliation: Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, the State Key Laboratory of Experimental Hematology, Tianjin 300020, China.
authors.forename: Z F
authors.initials: ZF
authors.lastname: Xu
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: J Q
authors.initials: JQ
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: X F
authors.initials: XF
authors.lastname: Ai
authors.forename: P H
authors.initials: PH
authors.lastname: Zhang
authors.forename: T J
authors.initials: TJ
authors.lastname: Qin
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: J Q
authors.initials: JQ
authors.lastname: Xu
authors.forename: H L
authors.initials: HL
authors.lastname: Zhang
authors.forename: L W
authors.initials: LW
authors.lastname: Fang
authors.forename: L J
authors.initials: LJ
authors.lastname: Pan
authors.forename: N B
authors.initials: NB
authors.lastname: Hu
authors.forename: S Q
authors.initials: SQ
authors.lastname: Qu
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D037282:Calreticulin / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2