DNMT3A Arg882 mutation drives chronic myelomonocytic leukemia through disturbing gene expression/DNA methylation in hematopoietic cells
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-BMT, all mice developed chronic myelomonocytic leukemia with thrombocytosis. RNA microarray analysis revealed abnormal expressions of some hematopoiesis-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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:111 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Jie [VerfasserIn] |
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| Links: |
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| Themen: |
Biological sciences |
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| PPN (Katalog-ID): |
JST113733151 |
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| 245 | 1 | 0 | |a DNMT3A Arg882 mutation drives chronic myelomonocytic leukemia through disturbing gene expression/DNA methylation in hematopoietic cells |
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| 520 | |a 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-BMT, all mice developed chronic myelomonocytic leukemia with thrombocytosis. RNA microarray analysis revealed abnormal expressions of some hematopoiesis-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. | ||
| 540 | |a copyright © 1993–2008 National Academy of Sciences of the United States of America | ||
| 650 | 4 | |a Biological sciences |x Biology |x Genetics |x Population genetics |x Genetic variation |x Genetic mutation | |
| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cells |x Cultured cells |x Cell lines |x 3T3 cells |x NIH 3T3 cells | |
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| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cells |x Stem cells | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Cancer |x Leukemia |x Myeloid leukemia | |
| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cells |x Stem cells |x Hematopoietic stem cells | |
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| 700 | 1 | |a Wang, Yue-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Yu-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei-Na |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Shu-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Zhao-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kan-Kan |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Sai-Juan |e verfasserin |4 aut | |
| 773 | 1 | 8 | |g volume:111 |g year:2014 |g number:7 |g pages:2620-2625 |
| 856 | 4 | 0 | |u https://www.jstor.org/stable/23768937 |3 Volltext |
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