Myeloid malignancy patient cells with 2 common splicing factor mutations, such as SF3B1^K700E and SRSF2^P95H/L/R mutations, are selected against. Selection can occur instead for cells with 2 splicing factor mutations that include less common alleles, such as SF3B1^non-K700E mutations (or rare amino acid changes at SRSF2 P95). Selection of cells with combined U2AF1^S34 and U2AF1^Q157 mutations has been shown when the 2 mutations occur in cis with preservation of 1 wild-type U2AF1 allele. WT, wild-type.