Gene mutations and their relationship with clinical features in 100 patients with myelodysplastic syndrome

Abstract

Objective To investigate the correlation between gene mutations and clinical features, prognosis, and the risk of acute myeloid leukemia (AML) transformation in patients with myelodysplastic syndrome (MDS). Methods We retrospectively analyzed clinical data from 100 MDS patients and next-generation sequencing（NGS） was employed to identify 34 MDS-associated gene mutations across all patients. The mutation rates and distributions were analyzed to assess the correlation of high-frequency mutations (≥10%) with clinical features, prognosis, and the risk of AML progression. Results NGS identified 32 types of gene mutations across the cohort, with 84% of patients harboring at least one mutation. Mutations were most frequently observed in the MDS-MLD subtypes (39.3%) and predominantly in patients aged ≥60 years（82.8%，53/64）. The ASXL1 gene exhibited the highest mutation ratio (26%), with TET2, U2AF1, DNMT3A, RUNX1, TP53, and SF3B1 also showing incidence higher than 10%. ASXL1 frequently co-mutated with RUNX1 and with TP53 exclusion. It revealed that higher percentages of bone marrow blasts were seen in ASXL1-positive patients, lower platelet counts in U2AF1-positive patients, and a greater prevalence of DNMT3A mutations in elderly patients (85.7%). RUNX1 mutations were associated with elevated white blood cell counts, while TP53 mutations correlated with higher IPSS-R scores（6 vs 4.5）(P=0.016 )and elevated LDH levels（P=0.002）（420 U/L vs 222 U/L）, respectively. The median follow-up period was 18.6 months, and the median overall survival was 27.1 months, with TP53 mutations being an independent predictor for poor overall survival (OS). During follow-up, 15% of patients progressed to AML, with DNMT3A mutations identified as an independent risk factor for AML transformation（HR=3.73）. Conclusions Genetic mutations are prevalent in MDS and correlate with distinct clinical features. In this cohort of MDS patients, the mutation rate of MDS-related genes is 84%. TP53 mutations were associated with poor prognosis, whereas DNMT3A mutations are linked to an increased risk of AML transformation.

Keywords

• |myelodysplastic syndromes|gene mutation|next-generation sequencing|prognosis|acute myeloid leukemia transformation