BCL2 Reins In BIM, Preventing Leukemic Cell Death

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Cancer / Oncology
Article Date: 05 Jan 2007 - 14:00 PDT

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Cancer is caused when a population of cells starts to grow in an inappropriate and uncontrolled manner. In many cancers the tumor cells express increased levels of a family of proteins (that includes BCL2 and MCL1) that protect them from a form of cell death known as apoptosis. Exactly how these proteins are important for tumor cell survival, and thereby inappropriate and uncontrolled growth, has not been completely clear.

In a study appearing in the January issue of the Journal of Clinical Investigation, Anthony Letai and colleagues from the Dana-Farber Cancer Institute in Boston developed a new technique, which they called 'BH3-profiling', to show that human chronic lymphocytic leukemia (CLL) cells depend on BCL2 for survival. CLL cells treated with a compound that antagonizes BCL2 (ABT-737) were found to undergo apoptosis. This compound was shown to work by disrupting the interaction of BCL2 with BIM, a protein that initiates apoptosis. The authors therefore suggest that the level of expression of anti-apoptotic BCL2 in a cell might not reliably predict the sensitivity of that cell to apoptosis-inducing stimuli, rather that the amount of free BCL2 able to mop up initiators of apoptosis such as BIM predicts this. In terms of CLL, if most BCL2 is bound to BIM then compounds such as ABT-737 that directly release the anti-apoptotic brake provided by BCL2 sequestration of BIM might provide effective therapeutics for the treatment of this cancer.

TITLE: Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737

AUTHOR CONTACT:

Anthony Letai,
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

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JCI table of contents: January 2, 2007

Contact: Brooke Grindlinger
Journal of Clinical Investigation

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