Clinical features and biological implications of different <i>U2AF1</i> mutation types in myelodysplastic syndromes

Abstract

Abstract U2AF1 mutations ( U2AF1 MT) occur commonly in myelodysplastic syndromes (MDS) without ring sideroblasts. The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS. We performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty‐six patients (17%) were found to have U2AF1 MT, which occurred more common in younger patients ( P = .001) and represented ancestral lesions in a substantial proportion (71%) of cases. ASXL1 MT and isolated +8 were significantly enriched in U2AF1 MT‐positive cases, whereas TP53 MT, SF3B1 MT, and complex karyotypes were inversely associated with U2AF1 MT. U2AF S34 subjects were enriched for isolated +8 and were inversely associated with complex karyotypes. U2AF1 MT was significantly associated with anemia, thrombocytopenia, and poor survival in both lower‐risk and higher‐risk MDS. U2AF1 S34 subjects had more frequently platelet levels of &lt;50 × 10 9 /L ( P = .043) and U2AF1 Q157 / U2AF1 R156 subjects had more frequently hemoglobin concentrations at &lt;80 g/L ( P = .008) and more often overt fibrosis ( P = .049). In conclusion, our study indicates that U2AF1 MT is one of the earliest genetic events in MDS patients and that different types of U2AF1 MT have distinct clinical and biological characteristics.