Pb1892: increased incidence of srsf2 mutation with age indicating clonal haematopoiesis in patients with acute myeloid leukaemia: a single-center experience

Topic: 4. Acute myeloid leukemia - Clinical Background: The serine and arginine rich splicing factor 2 (SRSF2) gene is frequently mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Based on the European Leukemia Net (ELN) 2022 risk stratification, SRSF2 mutation is classified as an adverse-risk genetic alteration in AML. Recent studies have suggested that SRSF2 mutation is age-related, with a higher prevalence in older AML patients. Aims: To determine the prevalence of SRSF2 mutation in a cohort of AML patients and to evaluate its association with age. Methods: We retrospectively analyzed the genetic data of 51 AML patients diagnosed between January 2018 and December 2022 at East Suffolk and North Essex foundation NHS trust. We performed targeted sequencing of 28 genes frequently mutated in AML using a custom-designed panel. The NGS technique used in this study involved extracting DNA from blood or bone marrow samples and utilizing a targeted TWIST panel to capture exons of 75 Haem-Onc genes. The Illumina NovaSeq was used for sequencing, and GATK and pindel were used for variant calling with a limit of detection of 5% variant allele frequency. The assay does not exclude the presence of variants outside the targeted regions or large insertions/deletions, gene copy number alterations, or gene rearrangements. Results: We found that the SRSF2 gene was mutated in 8 out of 51 patients (15.7%). All 8 patients were aged 60 years or above, with a median age of 73 years. The prevalence of SRSF2 mutation was significantly higher in older AML patients (≥60 years) than in younger patients (≤59 years) (26.7% vs 0%, p=0.028). According to the ELN 2022 risk stratification, all 8 patients with SRSF2 mutation were classified as having an adverse-risk genetic alteration. Summary/Conclusion: Our study confirms the high prevalence of SRSF2 mutation in AML patients, especially in older patients, and its association with adverse-risk group according to the ELN 2022 risk stratification. Given the poor prognosis associated with adverse-risk genetic alterations, SRSF2 mutation should be considered an important prognostic factor in the management of AML. Keywords: Acute myeloid leukemia, Age related clonal hematopoiesis, Mutation analysis, Somatic mutation