RNA splicing as a therapeutic target in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematological disorders and are more commonly found in people over the age of 60. MDS patients exhibit peripheral blood cytopenias and carry an increased risk of disease progression to acute myeloid leukemia (AML). Splicing factor mutations (including genes SF3B1, SRSF2, U2AF1, and ZRSR2) are early events identified in more than 50% of MDS cases. These mutations cause aberrant pre-mRNA splicing and impact MDS pathophysiology. Emerging evidence shows that splicing factor-mutant cells are more sensitive to perturbations targeting the spliceosome, aberrantly spliced genes and/or their regulated molecular pathways. This review summarizes current therapeutic strategies and ongoing efforts targeting splicing factor mutations for the treatment of MDS.