# Significance of Mutation Spots and Concurrent Gene Mutations on Prognosis and Clinical Outcomes in Myelodysplastic Syndromes With SF3B1 Mutation

## TL;DR

This study explores how specific SF3B1 mutations and accompanying gene changes affect the prognosis and clinical outcomes in myelodysplastic syndromes.

## Contribution

The study identifies distinct clinical features and survival differences based on SF3B1 mutation spots and concurrent gene mutations in MDS patients.

## Key findings

- The K700E mutation is the most common SF3B1 mutation in MDS patients.
- Patients with K666 mutations have worse clinical parameters like thrombocytopenia and lower NK cell percentages.
- E622 and H622 mutations are associated with better overall survival compared to K666 and R625 mutations.

## Abstract

To investigate the clinical characteristics and prognosis of mutation spots and concomitant gene mutations in myelodysplastic syndromes (MDS) with SF3B1 mutation (SF3B1

mut
).

Patients diagnosed with MDS at Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital from October 2008 to November 2023 were enrolled in this study. SF3B1

mut
was identified by next‐generation sequencing (NGS).

One hundred and seven (8.7%) cases harbored the SF3B1 mutation. The most frequent SF3B1

mut
, noted in 47.66% of all patients, was the hotspot K700E. K666 and R625 were observed in 24.30% and 9.35%, respectively. Two less frequent mutation subtypes accounted for 5.61% of H662 and 4.67% of E622. Patients with the K666 mutation showed more severe thrombocytopenia (p = 0.032), significantly lower NK cell percentage (p = 0.001), and the Th1/Th2 ratio (p = 0.018) in the bone marrow (BM). The overall survival (OS) in patients with E622 and H662 mutations was significantly longer than that of patients with the R625 mutation (p = 0.045) and the K666 mutation (p = 0.010). Multi‐variance analysis showed the SF3B1 mutation involving the K666 hotspot independently predicted overall survival in MDS (HR 2.094, p = 0.050). Notably, most (11/13, 84.6%) of concomitant TP53 mutations were mono‐hit, which did not affect the survival of patients in our cohort.

SF3B1

mut
patients with specific mutation spots and concomitant gene mutations showed distinct clinical features and prognosis. Consequently, a comprehensive study of specific subtypes is of great significance for improving the prognosis of patients with SF3B1 mutations.