[Mutation characteristics and prognosis of SF3B1-mutated myeloid neoplasms: an analysis of 183 patients].

Objective: To analyze the mutational characteristics and prognosis of patients with myeloid neoplasms and SF3B1 mutations. Methods: This retrospective cohort study analyzed clinical data from 183 patients with myeloid neoplasms and SF3B1 mutations diagnosed at the First Affiliated Hospital of Soochow University from October 2016 to December 2024. High-throughput sequencing was used to detect mutations in 52 common genes associated with myeloid neoplasms, and the patients' mutational characteristics were examined. Results: A total of 31 types of SF3B1 mutations were detected in the present study. SF3B1 mutations mainly occurred within the HEAT domain, spanning amino acids 581 to 933. The median number of gene mutations in patients with myelodysplastic neoplasms (MDS) [2 (1-7) ] was lower than that in patients with SF3B1-mutated myelodysplastic/myeloproliferative neoplasms (MDS/MPN) [4 (1-9) ] and acute myeloid leukemia (AML) [3 (1-9) ], with all differences being significant (all P<0.001). Among patients with clonal hematopoiesis and MDS with <5% blasts, those with an SF3B1 mutational variant allele frequency (VAF) of <10% had higher median HGB levels than those with an SF3B1 mutation VAF of ≥10% (95 g/L vs 76 g/L, P=0.002). Patients with an SF3B1 mutation VAF of <10% had a lower median percentage of ring sideroblasts than those with an SF3B1 mutation VAF of ≥10% (3% vs 41%, P<0.001). Furthermore, the incidence of JAK2 V617F mutations was higher in the MDS/MPN patients than in the MDS patients (22.2% vs 1.2%, P=0.001), as was the incidence of RUNX1 mutations (33.3% vs 6.6%, P=0.002). The incidence of RUNX1 mutation was higher in AML patients than in MDS patients (24.2% vs 6.6%, P=0.008), as was the RAS family gene mutations (66.7% vs 3.8%, P<0.001). In MDS and MDS/MPN, patients with RUNX1 mutations had a higher risk of progression to AML than those without such a mutation (P<0.001). Patients with MDS-SF3B1 (91.6%) and MDS/MPN (79.9%) demonstrated better 5-year overall survival than those with AML (63.8%) (P< 0.001 and P=0.033, respectively). Conclusion: Patients with different subtypes of SF3B1-mutated myeloid neoplasms exhibit distinct mutational profiles and prognoses.