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

Background Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but their clinical and prognostic relevance in acute myeloid leukemia (AML) have rarely 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 genomicDNA. The clinical features and survival were analyzed using statistical analysis. Results We found that 64 of 368 patients harbored SF mutations. The SF mutations were much more frequently found in older or male patients. SRSF2 mutations were shown obviously co-existed with IDH2 mutation. The level of measurable residual disease after 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 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 overall survival. SRSF2 mut was associated with older age, higher proportion of peripheral blasts or abnormal cell proportion by flow cytometry. Conclusion SF mutation is a distinct subgroup of AML frequently associated with clinic-biological features and poor outcome. SRSF2 mut could be potential targets for novel treatment in AML.