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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; 2/18/2014, Vol. 111 Issue 7, p2620-2625, 6p
- Publication Year :
- 2014
-
Abstract
- The gene encoding DNA methyltransferase 3A (DNMT3A) is mutated in ∼20% of acute myeloid leukemia cases, with Arg882 (R882) as the hotspot. Here, we addressed the transformation ability of the DNMT3A-Arg882His (R882H) mutant by using a retroviral transduction and bone marrow transplantation (BMT) approach and found that the mutant gene can induce aberrant proliferation of hematopoietic stem/progenitor cells. At 12 mo post-BWIT, all mice developed chronic myelomonocytic leukemia with thrombocytosis. RNA microarray analysis revealed abnormal expressions of some he-matopoiesis-related genes, and the DNA methylation assay identified corresponding changes in methylation patterns in gene body regions. Moreover, DNMT3A-R882H increased the CDK1 protein level and enhanced cell-cycle activity, thereby contributing to leukemogenesis. [ABSTRACT FROM AUTHOR]
- Subjects :
- METHYLATION
GENE expression
NUCLEIC acids
BONE marrow
ANEMIA
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 111
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 94712343
- Full Text :
- https://doi.org/10.1073/pnas.1400150111