Back to Search Start Over

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

Authors :
Szu-Chun Hsu
Bor-Sheng Ko
Shang-Ju Wu
Ming Yao
Chi-Cheng Li
Shang-Yi Huang
Yuan-Yeh Kuo
Cheng-Hong Tsai
Wen-Chien Chou
Hwei-Fang Tien
Chien-Ting Lin
Chien-Yuan Chen
Chia-Wen Liu
Jih-Luh Tang
Mei-Hsuan Tseng
Ming-Chih Liu
Ming-En Lin
Hsin-An Hou
Source :
Clinical Epigenetics, Vol 10, Iss 1, Pp 1-12 (2018), Clinical Epigenetics
Publication Year :
2018
Publisher :
BMC, 2018.

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. Electronic supplementary material The online version of this article (10.1186/s13148-018-0476-1) contains supplementary material, which is available to authorized users.

Details

Language :
English
ISSN :
18687083 and 18687075
Volume :
10
Issue :
1
Database :
OpenAIRE
Journal :
Clinical Epigenetics
Accession number :
edsair.doi.dedup.....1252787d11afdf5a94d29268db7f5eef
Full Text :
https://doi.org/10.1186/s13148-018-0476-1