Runx1 Deficiency Cooperates With Srsf2 Mutation To Further Disrupt Rna Splicing And Exacerbate Myelodysplastic Syndromes In Mouse Models

Myelodysplastic syndromes (MDS) and leukemias require the acquisition of multiple mutations during disease development resulting in clonal diversity and different responses. Splicing factors, transcription factors, epigenetic regulators, and cell signaling proteins are the common molecular events mutated during disease evolution and those events rarely occur alone. However, it remains unclear how the combinations of mutations in different categories may have cooperative effects in gene regulation and disease etiology. Mutations in the splicing factor SRSF2 and the transcription factor RUNX1 are closely associated in MDS patients, and their co-existence is linked to poor prognosis.