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New Test Predicts CLL’s Sensitivity to Experimental Drug

Dana-Farber Cancer Institute scientists have developed a test that is first to identify - which malignant blood cells are highly vulnerable to a promising// type of experimental drugs that unleash pent-up "cell suicide" factors to destroy the cancer.

The researchers demonstrated that chronic lymphocytic leukemia, CLL, which is diagnosed in 10,000 Americans each year, is an easy mark for the new drug because the cancerous cells are strongly dependent on a particular survival molecule, Bcl-2, that keeps the self-destruct signals at bay. They showed that the investigational drug neutralizes the Bcl-2 action, unleashing molecules that trigger suicide in the cancer cells, a process known as programmed cell death or apoptosis.

The research in the laboratory of Anthony Letai, MD, PhD, of Dana-Farber, is described in the January issue of The Journal of Clinical Investigation. The lead author is Victoria Del Gaizo Moore, PhD, a member of the Letai group.

Letai was a colleague of the late Stanley J. Korsmeyer, MD, of Dana-Farber, who discovered the key role in cancer played by anti-apoptosis molecules such as Bcl-2, which promote the survival of cells that are damaged or abnormal despite the body's efforts to eliminate them through apoptosis.

Inspired by this pioneering research, drug companies have begun testing novel Bcl-2 inhibiting drugs designed to restart the natural death processes thwarted by the survival molecule.

Letai said that his group has tested Abbott's investigational compound ABT-737 against cultured CLL cells with striking results. "We've treated CLL samples from several dozen patients, and each has responded to a very low concentration of the drug," said Letai. "We find it particularly interesting that the cells died within four hours."

Cells from CLL, a currently incurable disease, are vulnerable to this dramatic reversal of fortune because they are "primed for death;" they are survivi
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