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

被引：341

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

页码：120 / 125

页数：6

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