Dynamics of <italic>DNMT3A</italic> mutation and prognostic relevance in patients with primary myelodysplastic syndrome.

Background: <italic>DNMT3A</italic> gene mutation has been associated with poor prognosis in acute myeloid leukemia, but its clinical implications in myelodysplastic syndrome (MDS) and dynamic changes during disease progression remain controversial. Results: In this study, <italic>DNMT3A</italic> mutation was identified in 7.9% of 469 de novo MDS patients. <italic>DNMT3A</italic>-mutated patients had higher platelet counts at diagnosis, and patients with ring sideroblasts had the highest incidence of <italic>DNMT3A</italic> mutations, whereas those with multilineage dysplasia had the lowest incidence. Thirty-one (83.8%) of 37 <italic>DNMT3A</italic>-mutated patients had additional molecular abnormalities at diagnosis, and <italic>DNMT3A</italic> mutation was highly associated with mutations of <italic>IDH2</italic> and <italic>SF3B1</italic>. Patients with <italic>DNMT3A</italic> mutations had a higher risk of leukemia transformation and shorter overall survival. Further, <italic>DNMT3A</italic> mutation was an independent poor prognostic factor irrespective of age, IPSS-R, and genetic alterations. The sequential study demonstrated that the original <italic>DNMT3A</italic> mutations were retained during follow-ups unless allogeneic hematopoietic stem cell transplantation was performed, while <italic>DNMT3A</italic> mutation was rarely acquired during disease progression. Conclusions: <italic>DNMT3A</italic> mutation predicts unfavorable outcomes in MDS and was stable during disease evolutions. It may thus be a potential biomarker to predict prognosis and monitor the treatment response. [ABSTRACT FROM AUTHOR]