U2AF1 and acute myeloid leukemia: U2AF1 mutations rarely co-occur with other common splicing factor mutations (SRSF2, SF3B1, ZSZR2).40,41 In a cohort of 202 MDS/AML patients at Cleveland Clinic, only eight patients acquired comutations of U2AF1 and other splicing factors with variable variant allele frequency (VAF) in both hits (Fig.1B).