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). The gene discussed is SF3B1; the disease is acute myeloid leukemia.