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Blood. 2011 Aug 4;118(5):1329-39. doi: 10.1182/blood-2011-01-327197. Epub 2011 Jun 9.

Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells.

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1
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.

Abstract

Dependence on Bcl-2 proteins is a common feature of cancer cells and provides a therapeutic opportunity. ABT-737 is an antagonist of antiapoptotic Bcl-2 proteins and therefore is a good predictor of Bcl-x(L)/Bcl-2 dependence. Surprisingly, analysis of Mcl-1-dependent multiple myeloma cell lines revealed codependence on Bcl-2/Bcl-x(L) in half the cells tested. Codependence is not predicted by the expression level of antiapoptotic proteins, rather through interactions with Bim. Consistent with these findings, acquired resistance to ABT-737 results in loss of codependence through redistribution of Bim to Mcl-1. Overall, these results suggest that complex interactions, and not simply expression patterns of Bcl-2 proteins, need to be investigated to understand Bcl-2 dependence and how to better use agents, such as ABT-737.

PMID:
21659544
PMCID:
PMC3152498
DOI:
10.1182/blood-2011-01-327197
[Indexed for MEDLINE]
Free PMC Article

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