Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia
- Author(s)
- Glaser, SP; Lee, EF; Trounson, E; Bouillet, P; Wei, A; Fairlie, WD; Izon, DJ; Zuber, J; Rappaport, AR; Herold, MJ; Alexander, WS; Lowe, SW; Robb, L; Strasser, A;
- Details
- Publication Year 2012-01-15,Volume 26,Issue #2,Page 120-125
- Journal Title
- GENES & DEVELOPMENT
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
- Keywords
- MARROW-CELLS; STEM-CELLS; PROTEINS; GENE; CHEMOTHERAPY; EXPRESSION; SURVIVAL; BINDING; FAMILY; MICE
- Research Division(s)
- Cancer And Haematology; Molecular Genetics Of Cancer; Structural Biology
- Publisher's Version
- https://doi.org/10.1101/gad.182980.111
- Open Access at Publisher's Site
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- Copyright © 2012 by Cold Spring Harbor Laboratory Press
Creation Date: 2012-01-15 12:00:00