SF3B1, encoding the largest subunit of the splicing factor 3b protein complex, is crucial for spliceosome assembly and mRNA splicing [1]. It plays a significant role in regulating gene expression by ensuring proper pre-mRNA splicing, an essential process for normal cellular function and development.

Mutations in SF3B1 are frequently associated with hematological malignancies, especially myelodysplastic syndromes (MDS) [1,2,3,5,8]. In MDS, SF3B1 mutations are strongly linked to the presence of ring sideroblasts in the bone marrow [2]. SF3B1-mutant MDS is proposed as a distinct nosologic entity with a relatively good prognosis, and patients may respond to luspatercept, eliminating the transfusion requirement [3]. Additionally, SF3B1-mutant cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi) due to a defective replication stress response [4]. In MDS-RS, mis-splicing of coenzyme A synthase (COASY) induced by SF3B1 mutations affects heme biosynthesis and erythropoiesis, and supplementation with vitamin B5 can rescue these defects [6]. In ovarian cancer, inhibition of SF3B1 can improve the immune microenvironment through pyroptosis and synergize with αPDL1 [7].

In summary, SF3B1 is vital for mRNA splicing. Its mutations are closely related to hematological malignancies like MDS. Research on SF3B1-mutant models has revealed potential therapeutic vulnerabilities and new treatment strategies for these diseases, highlighting the importance of SF3B1 in understanding disease mechanisms and developing targeted therapies.