Research progress of U2AF1 mutations in patients with myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal diseases that originate from hematopoietic stem cells. The recurrence and development of MDS is a multi-step pathological process. Genetic mutations and epigenetic abnormalities are closely related to the initiation of MDS. Mutations in U2AF1 are identified as a higher frequency in MDS, which will lead to abnormal recognition of the pre-mRNA 3′splice site (3′SS) by the spliceosome and result in aberrant mRNA. Recently, intensive studies have shown that U2AF1 mutations are likely to be the early events of MDS and acute myeloid leukemia (AML), and patients with U2AF1 mutations have an inherent transformation to leukemia and low survival rate. Considering U2AF1 mutations and related molecular changes contributes to predict the clinical outcomes of patients with MDS. This review mainly discusses the molecular mechanisms of U2AF1 mutations and its functional significance, in order to provide theoretical basis to accelerate the discovery of new targeted treatments for MDS. Key words: Myelodysplastic syndromes; Splicing factor U2AF; Spliceosomes; Mutation; Prognosis