Researchers at the University of California, San Diego (UCSD) and the Moores UCSD Cancer Center have discovered what could be a novel drug target for an often difficult-to-treat form of leukemia. The investigators have identified a unique "signature" or pattern of a specific family of enzymes in patients with chronic lymphocytic leukemia (CLL), the most common form of adult leukemia.
Paul Insel, M.D., professor of pharmacology and medicine at the UC San Diego School of Medicine and his co-workers compared white blood cells in patients with CLL to those of healthy adults. They found that one form of the group of enzymes, collectively known as cyclic nucleotide phosphodiesterases, was 10 times higher in CLL patients than in normal individuals. The specific type of enzyme, phosphodiesterase 7B (PDE7B), controls the levels of cyclic AMP (cAMP), a molecule that can promote programmed cell death, a process that is defective in CLL. The team reports its findings this week in the Proceedings of the National Academy of Sciences.
Whereas most cancers have out-of-control cell growth, CLL is characterized by an overabundance of white blood cells that do not die when they should, Insel explained.
The scientists subsequently tested the effects of drugs that blocked PDE7B in CLL cells, and found that this raised cAMP levels and caused CLL cells to undergo cell death. He explained that since PDE7B degrades cAMP, blocking PDE7B in essence takes the clamp off of programmed cell death, enabling CLL cells to die.
"PDE7B is thus a new drug target for CLL," he said. "We have preliminary data from patient samples studied in the laboratory showing that we can increase the killing of CLL cells even more if we block PDE7B and also add other drugs used to treat CLL."
He noted that a test for PDE7B might also potentially be used as a way to detect CLL, though this has yet to be proven. CLL, which usually strikes adults over age 35, ha
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University of California - San Diego