September 28, 2025

SRSF2 gene mutation in patients with therapy-related myelodysplastic syndromes/acute myeloid leukemia

Key Points

Patients with therapy-related myelodysplastic syndromes showed a significant SRSF2 mutation presence compared to de novo cases.
Out of 47 patients with therapy-related myeloid neoplasms, 10 had positive SRSF2 mutations, indicating its potential prognostic value.
Patients with SRSF2 mutations had longer therapy exposure and shorter latency periods, suggesting the mutation's role in disease development.
This study enhances understanding of spliceosomal protein alterations, paving the way for new targeted treatments in affected patients.

Abstract

Introduction Therapy-related myeloid neoplasms (t-MNs) are a group of disorders arising due to somatic mutations induced by cytotoxic therapy. Recurrent somatic mutations in genes encoding spliceosomal proteins have been found throughout diverse cancer types. Serine/arginine-rich splicing factor 2 (SRSF2) plays a role in ensuring splicing accuracy and regulating alternative pre-mRNA splicing. Many studies have reported the potential prognostic value of SRSF2 mutation, which has an adverse prognostic impact on survival and disease progression. Patients and methods This study was a prospective study of t-MNs and de novo MNs. Genomic DNA was extracted from bone marrow or peripheral blood samples. A single pair of oligonucleotide primers was used to amplify the hotspot mutation region of the SRSF2 gene. Real-time PCR and high-resolution melting analysis of genomic DNA samples were performed on all patients. Results In this study, 47 patients with t-MNs and 44 patients with de novo MNs were included. A statistically significant difference was observed between two groups regarding the type of myeloid neoplasm (myelodysplastic syndrome or acute myeloid leukemia) with a P value less than 0.001. The results of SRSF2 gene mutation by high-resolution melting analysis showed that 10 patients with t-MNs had positive SRSF2 mutation, and 37 patients were negative for SRSF2 mutation. For the de novo acute myeloid leukemia patients, only seven patients were found to have a positive SRSF2 mutation. Patients with t-MNs with positive SRSF2 gene mutation had a longer duration of exposure to therapy for their primary malignancy ( P =0.002) and shorter latency period ( P =0.013) than t-MNs patients with negative results. Conclusion Defining the role of the splicing factor alterations in hematopoietic cells will provide a deeper insight into the molecular landscape of these mutations and pave the way for developing novel targeted drugs for individuals harboring this genetic signature.

AI에게 질문

Bookmark