The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice
文献类型:期刊论文
作者 | Deshpande, AJ; Rouhi, A; Lin, Y; Stadler, C; Greif, PA; Arseni, N; Opatz, S; Quintanilla-Fend, L; Holzmann, K; Hiddemann, W |
刊名 | LEUKEMIA
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出版日期 | 2011 |
卷号 | 25期号:11页码:1718-1727 |
关键词 | CALM AF10 acute myeloid leukemia |
通讯作者 | Buske, C (reprint author), Univ Ulm Klinikum, Inst Expt Tumorforsch CCC Ulm, Albert Einstein Allee 11, D-89081 Ulm, Germany.,christian.buske@uni-ulm.de |
英文摘要 | The t(10; 11)(p13-14;q14-21) translocation, giving rise to the CALM-AF10 fusion gene, is a recurrent chromosomal rearrangement observed in patients with poor prognosis acute myeloid leukemia (AML). Although splicing of the CALM-AF10 fusion transcripts has been described in AML patients, the contribution of different CALM and AF10 domains to in vivo leukemogenesis remains to be defined. We therefore performed detailed structure-function studies of the CALM-AF10 fusion protein. We demonstrate that fusion of the C-terminal 248 amino acids of CALM, which include the clathrin-binding domain, to the octapeptide motif-leucine-zipper (OM-LZ) domain of AF10 generated a fusion protein (termed CALM-AF10 minimal fusion (MF)), with strikingly enhanced transformation capabilities in colony assays, providing an efficient system for the expeditious assessment of CALM-AF10-mediated transformation. Leukemias induced by the CALM-AF10 (MF) mutant recapitulated multiple aspects of full-length CALM-AF10-induced leukemia, including aberrant Hoxa cluster upregulation, a characteristic molecular lesion of CALM-AF10 leukemias. In summary, this study indicates that collaboration of the clathrin-binding and the OM-LZ domains of CALM-AF10 is sufficient to induce AML. These findings further suggest that future approaches to antagonize CALM-AF10-induced transformation should incorporate strategies, which aim at blocking these key domains. Leukemia (2011) 25, 1718-1727; doi:10.1038/leu.2011.153; published online 17 June 2011 |
学科主题 | Oncology; Hematology |
类目[WOS] | Oncology ; Hematology |
关键词[WOS] | ACUTE LYMPHOBLASTIC-LEUKEMIA ; CALM/AF10 FUSION ; LEUCINE-ZIPPER ; SUBCELLULAR-LOCALIZATION ; MLL-MLLT10 FUSION ; ASSEMBLY PROTEIN ; STEM-CELL ; CALM-AF10 ; MLL ; GENE |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000296922100007 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/867] ![]() |
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 | Deshpande, AJ,Rouhi, A,Lin, Y,et al. The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice[J]. LEUKEMIA,2011,25(11):1718-1727. |
APA | Deshpande, AJ.,Rouhi, A.,Lin, Y.,Stadler, C.,Greif, PA.,...&Buske, C.(2011).The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice.LEUKEMIA,25(11),1718-1727. |
MLA | Deshpande, AJ,et al."The clathrin-binding domain of CALM and the OM-LZ domain of AF10 are sufficient to induce acute myeloid leukemia in mice".LEUKEMIA 25.11(2011):1718-1727. |
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