Frequency and phenotypic association of spliceosomal mutations in myeloid malignancies. (A) In the entire cohort (n = 310), a total of 88 mutations in the spliceosome pathway components U2AF1, SF3B1, and SRSF2 were observed in every subtype of myeloid malignancies, except for MPN. In low-risk MDS, SF3B1 mutations were most frequent among the 3 genes. In particular, SF3B1 was mutated in 15 of 20 cases of RARS (60%). In the high-risk MDS and AML group, U2AF1 mutations were most frequent (15 of 139; 10.8%). In the MDS/MPN group, SRSF2 was most frequently mutated (13 of 46; 28.2%), whereas SF3B1 is mutated at a high frequency in RARS-T (10 of 11; 90.1%). (B) Effect of spliceosomal mutations on clinical outcomes. In the entire cohort, patients with U2AF1 mutations (MT) had worse OS, compared with WT, but SF3B1 mutations made OS significantly shorter. In low-risk MDS, mutation of SF3B1 was a good prognostic factor, but SRSF2 mutations are associated with worse prognosis. In MDS/MPN, patients with mutated U2AF1 had a shorter OS, but SF3B1 mutations were associated with significantly better prognosis. In addition, SRSF2 mutations did not affect outcomes.