Molecular Threat of Splicing Factor Mutations to Myeloid Malignancies and Potential Therapeutic Modulations

Abstract

Splicing factors are frequently mutated in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations are presumed to contribute to oncogenic transformation, but the underlying mechanisms remain incompletely understood. While no specific treatment option is available for MDS/AML patients with spliceosome mutations, novel targeting strategies are actively explored, leading to clinical trials of small molecule inhibitors that target the spliceosome, DNA damage response pathway, and immune response pathway. Here, we review recent progress in mechanistic understanding of splicing factor mutations promoting disease progression and summarize potential therapeutic strategies, which, if successful, would provide clinical benefit to patients carrying splicing factor mutations.