Dynamics of DNMT3A mutation and prognostic relevance in patients with primary myelodysplastic syndrome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Ming-En Lin, Hsin-An Hou, Cheng-Hong Tsai, Shang-Ju Wu, Yuan-Yeh Kuo, Mei-Hsuan Tseng, Ming-Chih Liu, Chia-Wen Liu, Wen-Chien Chou, Chien-Yuan Chen, Jih-Luh Tang, Ming Yao, Chi-Cheng Li, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Chien-Ting Lin, Hwei-Fang Tien

ABSTRACT

Background: DNMT3A 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, DNMT3A mutation was identified in 7.9% of 469 de novo MDS patients. DNMT3A-mutated patients had higher platelet counts at diagnosis, and patients with ring sideroblasts had the highest incidence of DNMT3A mutations, whereas those with multilineage dysplasia had the lowest incidence. Thirty-one (83.8%) of 37 DNMT3A-mutated patients had additional molecular abnormalities at diagnosis, and DNMT3A mutation was highly associated with mutations of IDH2 and SF3B1. Patients with DNMT3A mutations had a higher risk of leukemia transformation and shorter overall survival. Further, DNMT3A mutation was an independent poor prognostic factor irrespective of age, IPSS-R, and genetic alterations. The sequential study demonstrated that the original DNMT3A mutations were retained during follow-ups unless allogeneic hematopoietic stem cell transplantation was performed, while DNMT3A mutation was rarely acquired during disease progression. Conclusions: DNMT3A 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. More... »

PAGES

42

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13148-018-0476-1

    DOI

    http://dx.doi.org/10.1186/s13148-018-0476-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1101888186

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29619119


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