Preferential occurrence of spliceosome mutations in acute myeloid leukemia with preceding myelodysplastic syndrome and/or myelodysplasia morphology

Abstract

Spliceosome mutations are associated with myelodysplasia. Here, we aimed to evaluate the frequency and clinical associations of these mutations in 204 patients with acute myeloid leukemia with myelodysplasia-related changes (AML with MRC) and 37 with therapy-related AML (t-AML). The frequency of mutation-positive patients was 17.0%, including U2AF1 (8.3%), SRSF2 (5.8%) and SF3B1 (2.9%). Mutations were detected almost exclusively in patients with AML with MRC, especially in cases with a preceding myelodysplastic syndrome (MDS) history or myelodysplastic morphology. By contrast, mutations were rare in patients with only MDS-related cytogenetics or t-AML. The presence of a mutation had no impact on survival. In a paired analysis, 16.7% of mutation-negative patients in the MDS phase acquired mutations during leukemogenesis. Our observations highlight the preponderance of spliceosome mutations within a specific AML subgroup with myelodysplasia, and suggest that these mutations might contribute pathologically to leukemogenesis in such patients.