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

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.