[Clinical Characteristics and Prognosis Analysis of MDS-RS Patients with Wild-Type SF3B1]

To explore the clinical features and prognosis of myelodysplastic syndrome with ring sideroblasts (MDS-RS) patients with wild-type splicing factor 3B subunit 1 (SF3B1 ).

The bone marrow samples from 132 patients with MDS-RS who were initially diagnosed at Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine from January 2009 to February 2021 were collected. Next generation sequencing (NGS)was used to obtain gene mutation information of patients (covering all core mutation genes of MDS), with a particular focus on analyzing the clinical characteristics, co-mutation profiles, and prognosis of MDS-RS patients with wild-type SF3B1 .

Among the 132 MDS-RS patients, 50 cases (37.9%) were negative for SF3B1 mutations, of which 39 patients (78%) had concurrent mutations in other genes. The common accompanying mutations were TP53 (15 cases), DNMT3A (10 cases), U2AF1 (8 cases), TET2 (7 cases), ASXL1 (7 cases), and RUNX1 (6 cases), and SETBP1 (3 cases). In the 82 cases (62.1%) who were positive for SF3B1 mutations, the highest occurrence frequency was SF3B1 K700E mutation (42 cases). Additionally, 57 patients (69.51%) had concurrent mutations in other genes, with the top three highest mutation frequencies observed in ASXL1 (13 cases), DNMT3A (11 cases), and RUNX1 (7 cases). Compared to patients with SF3B1 mutations, those with wild-type SF3B1 exhibited significant pancytopenia and higher risk of IPSS-R and IPSS-M prognostic scores. The median overall survival (OS) of patients with wild-type SF3B1 was 22 months, which was significantly shorter than 55 months of SF3B1 mutated patients (P < 0.05), and they also had a higher risk of transformation to acute myeloid leukemia (AML) (P < 0.05). Multivariate analysis revealed that SF3B1 mutation was not an independent prognostic factor affecting MDS-RS, and its prognostic value might be influenced by mutation sites, co-mutations, and other factors.

Patients with wild-type SF3B1 have a significantly shorter OS compared to those with SF3B1 mutations, and they also have a higher risk of transformation to AML, which may be associated with TP53 mutations.