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