JAK2、MPL和CALR基因突变在中国原发性骨髓纤维化患者中的预后意义

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 74 vs 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). CONCLUSION: 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.