Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia

被引：338
|
作者：
Glaser, Stefan P. [1 ,2 ]
Lee, Erinna F. [1 ,2 ]
Trounson, Evelyn [1 ]
Bouillet, Philippe [1 ,2 ]
Wei, Andrew [3 ,4 ]
Fairlie, W. Douglas [1 ,2 ]
Izon, David J. [5 ]
Zuber, Johannes [6 ,7 ]
Rappaport, Amy R. [6 ,8 ]
Herold, Marco J. [1 ,2 ]
Alexander, Warren S. [1 ,2 ]
Lowe, Scott W. [6 ,8 ,9 ]
Robb, Lorraine [1 ,2 ]
Strasser, Andreas [1 ,2 ]
机构：
[1] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia
[2] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia
[3] Alfred Hosp, Australian Ctr Blood Dis, Melbourne, Vic 3004, Australia
[4] Monash Univ, Melbourne, Vic 3004, Australia
[5] St Vincents Inst, Fitzroy, Vic 3065, Australia
[6] Cold Spring Harbor Labs, Cold Spring Harbor, NY 11724 USA
[7] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria
[8] Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA
[9] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA
来源：
GENES & DEVELOPMENT | 2012年 / 26卷 / 02期
基金：
澳大利亚国家健康与医学研究理事会;
关键词：
acute myeloid leukemia; apoptosis; Mcl-1; Bcl-x(L); MARROW-CELLS; STEM-CELLS; PROTEINS; GENE; CHEMOTHERAPY; EXPRESSION; SURVIVAL; BINDING; FAMILY; MICE;
D O I：
10.1101/gad.182980.111
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Acute myeloid leukemia (AML) frequently relapses after initial treatment. Drug resistance in AML has been attributed to high levels of the anti-apoptotic Bcl-2 family members Bcl-x(L) and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-x(L), Bcl-2, or Bcl-w, caused the death of transformed AML and could cure disease in AML-afflicted mice. Enforced expression of selective inhibitors of prosurvival Bcl-2 family members revealed that Mcl-1 is critical for survival of human AML cells. Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML.
引用
收藏
页码：120 / 125
页数：6
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