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DNMT3A Arg882 mutation drives chronic myelomonocytic leukemia through disturbing gene expression/DNA methylation in hematopoietic cells
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 111(7)
- Publication Year :
- 2014
-
Abstract
- Significance Epigenetic modifications are required for the regulation of hematopoiesis. DNA methyltransferase 3A (DNMT3A), a critical epigenetic modifier responsible for de novo DNA methylation, was reported recently to be a frequently mutated gene in hematopoietic malignancies. However, the role of mutated DNMT3A in hematopoiesis remains largely unknown. Here we show that the Arg882 (R882) mutation of DNMT3A disrupts the normal function of this enzyme and results in chronic myelomonocytic leukemia (CMML) in mice. Meanwhile, the gene expression, DNA methylation, and protein–protein interaction assays suggest that DNMT3A R882 mutation drives CMML by disturbing the transcriptional expression/DNA methylation program and cell-cycle regulation of hematopoietic cells. This study may shed light on the function of DNMT3A mutant in myeloid leukemogenesis.
- Subjects :
- Blotting, Western
Immunoblotting
Mutation, Missense
Chronic myelomonocytic leukemia
Biology
Mass Spectrometry
DNA Methyltransferase 3A
Immunophenotyping
Mice
Gene expression
medicine
Animals
Humans
Immunoprecipitation
DNA (Cytosine-5-)-Methyltransferases
Epigenomics
Regulation of gene expression
Mice, Inbred BALB C
Multidisciplinary
Gene Expression Profiling
Cell Cycle
Myeloid leukemia
Leukemia, Myelomonocytic, Chronic
Methylation
DNA Methylation
Biological Sciences
medicine.disease
Flow Cytometry
Hematopoietic Stem Cells
Microarray Analysis
Molecular biology
Gene expression profiling
Gene Expression Regulation
DNA methylation
embryonic structures
Cancer research
Mutagenesis, Site-Directed
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 111
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....3e7e88b6133f588d7a4a32fdc517f93c