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Dynamics of DNMT3A mutation and prognostic relevance in patients with primary myelodysplastic syndrome
- 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.
- Subjects :
- Male
0301 basic medicine
Oncology
medicine.medical_treatment
lcsh:Medicine
Disease
Hematopoietic stem cell transplantation
DNA Methyltransferase 3A
0302 clinical medicine
Medicine
DNA (Cytosine-5-)-Methyltransferases
Genetics (clinical)
Aged, 80 and over
Incidence (epidemiology)
Myeloid leukemia
Middle Aged
Prognosis
Leukemia
030220 oncology & carcinogenesis
Mutation (genetic algorithm)
embryonic structures
Disease Progression
Paired samples
Adult
medicine.medical_specialty
Adolescent
lcsh:QH426-470
IDH2
Young Adult
03 medical and health sciences
Internal medicine
Genetics
Humans
Molecular Biology
Aged
business.industry
Research
lcsh:R
Sequence Analysis, DNA
medicine.disease
Survival Analysis
Human genetics
lcsh:Genetics
030104 developmental biology
Myelodysplastic Syndromes
Mutation
DNMT3A
business
Myelodysplastic syndrome
Developmental Biology
Subjects
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