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New Method For Fighting Leukemia

Researchers at Virginia Commonwealth University's Massey Cancer Center have created a new method for fighting Leukemia.

This new method improves the antileukemic activity of a novel agent that triggers programmed cell death, //a development that could lead to more effective strategies for fighting leukemia and other malignancies.

The cell death process, or apoptosis, is characteristically impaired in cancer cells. The process is regulated by a large family of proteins that either promotes or inhibits cell death. Recently, considerable attention has focused on the development of agents that inhibit the actions of antiapoptotic members of this family.

One such agent, known as ABT-737, potently blocks the pro-survival effects of two proteins, Bcl-2 and Bcl-xL, according to Steven Grant, M.D., Massey's associate director for translational research and co-leader of the cancer center's cancer cell biology program. Grant is senior author of the study, which is published in the Jan. 15 issue of the journal Cancer Research.

In laboratory experiments, ABT-737 has been shown to be very effective in killing tumor cells. However, this agent is unable to block the actions of another anti-apoptotic family member, Mcl-1, and it has been found that increased expression of Mcl-1 in tumor cells significantly reduces the anti-tumor effectiveness of ABT-737.

Grant and colleagues demonstrated that interventions that reduce levels of Mcl-1 in leukemia cells dramatically increase the effectiveness of ABT-737. Specifically, they employed an agent called roscovitine to block the synthesis of Mcl-1 at the RNA level. Grant said that because Mcl-1 is a very short-lived protein, disrupting its synthesis rapidly lowers Mcl-1 levels.

Grant's team found that the simultaneous reduction in Mcl-1 expression in conjunction with disruption of the anti-apoptotic actions of Bcl-2 and Bcl-xL by ABT-737 resulted in the marked activati
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