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

Year: 2012
Type: preprint
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.
DOI: 10.1101/gad.182980.111
Authors: Stefan P. Glaser, Erinna F. Lee, Evelyn Trounson, Philippe Bouillet, Andrew Wei, W. Douglas Fairlie, David J. Izon, Johannes Zuber, Amy R. Rappaport, Marco J. Herold, Warren S. Alexander, Scott W. Lowe, Lorraine Robb, Andreas Strasser
Institutions: The University of Melbourne, Walter and Eliza Hall Institute of Medical Research, The Alfred Hospital, Monash University, Research Institute of Molecular Pathology, Cold Spring Harbor Laboratory, Memorial Sloan Kettering Cancer Center
Language: English
Open Access status: diamond
Funders: Leukemia and Lymphoma Society, Victorian Cancer Agency, Lady Tata Memorial Trust, Australian Government, Deutsche Forschungsgemeinschaft, National Institutes of Health, Stanford Institute for Research in the Social Sciences, National Health and Medical Research Council, National Cancer Institute
Awards: The cellular life/death switch, Cell death and leukaemia, G205107959, G299033074, Cell Death and Stem Cells in Cancer and Its Therapy, G530122211, Develop new approaches to cancer diagnosis and treatment, Control of white blood call production and function, IRIISS, G7703980830
OpenAlex ID: W2171224722
Cites: 30
Cited by: 423
Related to: 10