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.