Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias
文献类型：期刊论文
| 作者 | Lin, YH; Kakadia, PM; Chen, Y; Li, YQ; Deshpande, AJ; Buske, C; Zhang, KL; Zhang, Y; Xu, GL; Bohlander, SK |
| 刊名 | BLOOD
 |
| 出版日期 | 2009 |
| 卷号 | 114期号:3页码:651-658 |
| 通讯作者 | Bohlander, SK (reprint author), KKG Leukemia Haematol, Klinikum Grosshadern Raum 003, Med Klin & Poliklin 3, GSF Marchioninistr 25, D-81377 Munich, Germany.,glxu@sibs.ac.cn ; stefan.bohlander@med.uni-muenchen.de |
| 英文摘要 | Chromosomal translocations generating fusion proteins are frequently found in human leukemias. The fusion proteins play an important role in leukemogenesis by subverting the function of one or both partner proteins. The leukemogenic CALM-AF10 fusion protein is capable of interacting with the histone H3 lysine 79 ( H3K79)-specific methyltransferase hDOT1L through the fused AF10 moiety. This interaction leads to local H3K79 hypermethylation on Hoxa5 loci, which up-regulates the expression of Hoxa5 and contributes to leukemogenesis. However, the long latency of leukemogenesis of CALM-AF10 transgenic mice suggests that the direct effects of fusion oncogene are not sufficient for the induction of leukemia. In this study, we show that the CALM-AF10 fusion protein can also greatly reduce global H3K79 methylation in both human and murine leukemic cells by disrupting the AF10-mediated association of hDOT1L with chromatin. Cells with reduced H3K79 methylation are more sensitive to gamma-irradiation and display increased chromosomal instability. Consistently, leukemia patients harboring CALM-AF10 fusion have more secondary chromosomal aberrations. These findings suggest that chromosomal instability associated with global epigenetic alteration contributes to malignant transformation in certain leukemias, and that leukemias with this type of epigenetic alteration might benefit from treatment regimens containing DNA-damaging agents. This study is registered with www.clinicaltrials.gov as NCT00266136. (Blood. 2009; 114: 651-658) |
| 学科主题 | Hematology |
| 类目[WOS] | Hematology |
| 关键词[WOS] | ACUTE MYELOID-LEUKEMIA ; DOUBLE-STRAND BREAKS ; HISTONE H3 ; MAMMALIAN-CELLS ; T(10-11) TRANSLOCATION ; GENE-EXPRESSION ; MLL-ELL ; FUSION ; LEUKEMOGENESIS ; PROTEIN |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000268061800026 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1161]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Lin, YH,Kakadia, PM,Chen, Y,et al. Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias[J]. BLOOD,2009,114(3):651-658. |
| APA | Lin, YH.,Kakadia, PM.,Chen, Y.,Li, YQ.,Deshpande, AJ.,...&Bohlander, SK.(2009).Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias.BLOOD,114(3),651-658. |
| MLA | Lin, YH,et al."Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias".BLOOD 114.3(2009):651-658. |
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