Clinical and prognostic profile of SRSF2 and related spliceosome mutations in patients with acute myeloid leukemia

Abstract Background Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but rare data about the clinical and prognostic relevance of these mutations in acute myeloid leukemia (AML) have been reported. Methods A total of 368 newly diagnosed non-M3 AML patients were included in this study. Next generation sequencing including four SF genes was performed on the genomic DNA. The clinical features and survival were analyzed using statistical analysis. SRSF2P95H function was assessed by CCK8 assay. Results We found that 64 of 368 patients harbored SF mutations. The SF mutations were much more frequent in older or male patients compared with SF-wild patients. SRSF2 mutations were shown obviously co-existed with IDH2 mutation. The level of measurable residual disease after the first chemotherapy was higher in SF-mutated patients compared to that in SF-wild patients, while the complete remission rate was significantly decreased. And the overall survival (OS) of SF-mutated patients was shorter than that of SF-wild patients. Moreover, our multivariable analysis suggests that the index of male, Kit mutation or ZRSR2 mutation was the independent risk factor for OS. SRSF2mut was associated with older age, higher proportion of peripheral blasts or abnormal cell proportion by FCM (Flow CytoMetry). Functionally, the mutation of SRSF2P95H significantly promoted the proliferation of AML cells. Conclusion Spliceosome mutation is a distinct subgroup of AML frequently associated with clinic-biological features and poor outcome. SRSF2mut could be potential targets for novel treatment in AML.