Non-driver gene mutation analysis in a large cohort of polycythemia vera and essential thrombocythemia

Objectives A proportion of patients with polycythemia vera (PV) and essential thrombocythemia (ET) harbor non-driver mutations associated with poor prognosis. In this study, we analyzed the frequency of non-driver mutations in a large Japanese PV and ET cohort. Furthermore, we studied the relationship of these mutations and prognosis in Japanese patients. Methods We enrolled 843 Japanese patients with PV or ET. Non-driver mutations were analyzed by target resequencing using next-generation sequencing. The association of the mutations with the prognosis was estimated using multivariable logistic regression analysis and log-rank test. Results Non-driver mutations were detected in 31.1% and 24.5% patients with PV and ET, respectively. Among them, ASXL1 mutations were identified as a risk factor for leukemic/myelofibrotic transformation in PV and ET patients (hazard ratio: 4.68, p = .006). The higher-risk groups of the mutation-enhanced international prognostic system (MIPSS)-PV and MIPSS-ET incorporating non-driver mutations exhibited significantly shorter overall survival compared with the low-risk group (p < .001). Conclusions These results implicate the importance of studying non-driver mutations for predicting the prognosis and survival of Japanese PV and ET patients.

Automated summary

In this study, the frequency of non-driver mutations in a large Japanese PV and ET cohort was analyzed, and their relationship with prognosis in Japanese patients was studied. ASXL1 mutations were identified as a risk factor for leukemic/myelofibrotic transformation, and the high-risk groups of the mutation-enhanced international prognostic system (MIPSS)-PV and MIPSS-ET exhibited significantly shorter overall survival. These findings highlight the importance of studying non-driver mutations for predicting the prognosis and survival of Japanese PV and ET patients.