Journal article
Anti-apoptotic mcl-1 is essential for the development and sustained growth of acute myeloid leukemia
SP Glaser, EF Lee, E Trounson, P Bouillet, A Wei, WD Fairlie, DJ Izon, J Zuber, AR Rappaport, MJ Herold, WS Alexander, SW Lowe, L Robb, A Strasser
Genes and Development | Published : 2012
Open access
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-xL and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-xL, 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. © 2012 by Cold Spring Harbor Laboratory Press.
Grants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Drs. L. Hennighausen, J.M. Adams, S. Cory, D. C. S. Huang, M. Cleary, D.-E. Zhang, C. Largman, and M. Busslinger for gifts of mice and retroviral constructs. This work was supported by grants and fellowships from the Deutsche Forschungsgemeinschaft (DFG) (to S. G.), the Lady Tata Memorial Trust (to S. G.), the NHMRC (programs 257500 and 461221; projects 637326 and 1008329; fellowships 356203, 461299, and 575501; and Independent Research Institutes Infrastructure Support Scheme grant 361646), the Leukemia and Lymphoma Society (SCOR grant 7413), the NIH (CA43540 and CA80188), the Victorian Cancer Agency, the Leukemia Foundation of Australia, and the Australian Cancer Research Fund, and by operational infrastructure grants through the Australian Government (IRISS) and the Victorian State Government (OIS).