Alteration of SF3B1 and SRSF2 Genes in Myelodysplastic Syndromes Patients in Upper Northern Thailand

Abstract

Background: The frequency and pattern of mutation in SF3B1 and SRSF2 RNA splicing machinery genes were<br />found to vary among myelodysplastic syndrome (MDS) patients in different populations. There have been less reports<br />of incidence of these gene mutations in Thailand especially in upper northern Thailand. This study therefore had aims<br />to investigate the frequency and pattern of mutation in mutational hotspot of SF3B1 and SRSF2 genes among MDS<br />patients in upper northern Thailand and to investigate the clinical features associated with the mutations. Methods:<br />Fifty-five MDS patients who underwent treatment at Maharaj Nakorn Chiang Mai Hospital participated in this study.<br />The detection of SF3B1 and SRSF2 hotspot mutations was carried out using polymerase chain reaction followed by<br />Sanger sequencing. In addition, clinical features of individual patients with these gene mutations were also investigated.<br />Results: SF3B1 mutations (SF3B1mut) were found in 9 patients (16.4%) including E622D (1/9), R625C (1/9), H662Q<br />(1/9), K700E (5/9), and Q699H co-mutation with K700E (1/9). SRSF2 mutations (SRSF2mut) were found in 4 patients<br />(7.3%) which included P95H (3/4) and P95L (1/4). The SF3B1mut was associated with lower hemoglobin levels (p = 0.023)<br />and higher platelet counts (p = 0.047) when compared with MDS patients without SF3B1mut, while SRSF2mut tended<br />to occur in patients with a higher percentage of bone marrow blasts (p = 0.074). Conclusion: The findings confirmed<br />the difference in frequency of SF3B1 and SRSF2 mutations among different populations. Specifically, we found a<br />co-mutation of Q699H and K700E that has not been previously reported in MDS patients in the COSMIC database.<br />It was also found that SF3B1mut was strongly associated with low hemoglobin level, and high platelet counts whereas<br />SRSF2mut was mostly clustered in MDS with excess blasts subsequently increasing the probability of progression to<br />acute myeloid leukemia.