Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia.
Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia.
复制标题
抑制线粒体翻译是人类急性髓样白血病的治疗策略。
DOI：
10.1016/j.ccr.2011.10.015
复制
发表时间：
2011-11-15
期刊：
影响因子：
50.3
通讯作者：
Schimmer AD
中科院分区：
文献类型：
--
作者：
Skrtić M;Sriskanthadevan S;Jhas B;Gebbia M;Wang X;Wang Z;Hurren R;Jitkova Y;Gronda M;Maclean N;Lai CK;Eberhard Y;Bartoszko J;Spagnuolo P;Rutledge AC;Datti A;Ketela T;Moffat J;Robinson BH;Cameron JH;Wrana J;Eaves CJ;Minden MD;Wang JC;Dick JE;Humphries K;Nislow C;Giaever G;Schimmer AD
为了鉴定FDA批准的靶向白血病细胞的药物，我们对两种人白血病细胞系进行了化学筛选，并鉴定了抗微生物剂替加环素。在酵母中进行的全基因组筛选确定线粒体翻译抑制是替加氯铵介导的致死性机制。替加环素选择性地杀死白血病干细胞和祖细胞相比，他们的正常同行，也显示出抗白血病小鼠模型中的人类白血病活性。shRNA介导的白血病细胞中EF-Tu线粒体翻译因子的敲低再现了替加环素的抗白血病活性。这些效应是线粒体生物发生的衍生物，与增加的基础耗氧量一起，证明在AML与正常造血细胞中增强，并且对于替加环素敏感性的差异也很重要。
To identify FDA-approved agents targeting leukemic cells, we performed a chemical screen on two human leukemic cell lines and identified the antimicrobial tigecycline. A genome-wide screen in yeast identified mitochondrial translation inhibition as the mechanism of tigecycline-mediated lethality. Tigecycline selectively killed leukemia stem and progenitor cells compared to their normal counterparts and also showed anti-leukemic activity in mouse models of human leukemia. ShRNA-mediated knockdown of EF-Tu mitochondrial translation factor in leukemic cells reproduced the anti-leukemia activity of tigecycline. These effects were derivative of mitochondrial biogenesis which, together with an increased basal oxygen consumption, proved to be enhanced in AML versus normal hematopoietic cells and were also important for their difference in tigecycline sensitivity.
登录
查看更多内容
影响因子：
4.8
作者：
Li, NY;Ragheb, K;Robinson, JP
通讯作者：
Robinson, JP
影响因子：
4.8
作者：
Koc, EC;Spremulli, LL
通讯作者：
Spremulli, LL
影响因子：
64.5
作者：
Gupta PB;Onder TT;Jiang G;Tao K;Kuperwasser C;Weinberg RA;Lander ES
通讯作者：
Lander ES
影响因子：
4.9
作者：
McKee, EE;Ferguson, M;Marks, TA
通讯作者：
Marks, TA
DOI：
10.1073/pnas.0700690104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Funes, Juan M.;Quintero, Marisol;Boshoff, Chris
通讯作者：
Boshoff, Chris