Murine models with conditional heterozygous expression of splicing factor (SF) mutations (SF3B1, U2AF1, SRSF2, ZRSR2) have confirmed the causative effects of RNA splicing dysregulation in the pathogenesis of myeloid malignancies and CLL (5, 30, 42–45). Here, U2AF1 is linked to B-cell chronic lymphocytic leukemia.