Researchers identify potential new drug target for chronic leukemia

Nov 24, 2008

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, has two major forms. One form progresses slowly, with few symptoms for years, and can be difficult to detect. The other form is more aggressive and dangerous. No one knows what makes one form different from the other. Current therapies have limited effectiveness, especially once the disease is in its aggressive phase.

The researchers are planning to screen potential drugs to treat CLL based on the PDE7B-cAMP connection. They are also exploring other potential treatment strategies to increase cAMP or disrupt its breakdown.

"We think that CLL cells may have found ways to help keep themselves alive by preventing cAMP from increasing," Insel said. "This paper provides a validation of the importance of the cAMP pathway as a target for drugs that might be used to treat CLL."

Source: University of California - San Diego

Explore further: Survival differences seen for advanced-stage laryngeal cancer

add to favorites email to friend print save as pdf

Related Stories

New biomarker may predict leukemia aggressiveness

Apr 19, 2009

Scientists at the University of California, San Diego and the Moores UCSD Cancer Center have evidence of a potential new biomarker to predict the aggressiveness of an often difficult-to-treat form of leukemia. They found ...

Recommended for you

Survival differences seen for advanced-stage laryngeal cancer

23 hours ago

The five-year survival rate for advanced-stage laryngeal cancer was higher than national levels in a small study at a single academic center performing a high rate of surgical therapy, including a total laryngectomy (removal ...

Gene test aids cancer profile

Nov 27, 2014

The first round of chemotherapy did little to suppress Ron Bose's leukemia. The second round, with 10 times the dose, knocked the proliferating blast cells down, but only by half.

Hospital volume not linked to costs of cancer surgery

Nov 26, 2014

(HealthDay)—Hospital surgical volume does not appear to correlate with Medicare payments for cancer surgery, according to research published online Nov. 24 in the Journal of Clinical Oncology.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.