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Apr 20, 2009

High Enzyme Levels May Indicate That Chronic Lymphocytic Leukemia Will Be Aggressive

  • Scientists at the University of California, San Diego and the Moores UCSD Cancer Center discovered a potential new biomarker to differentiate between cases of aggressive and more dangerous chronic lymphocytic leukemia (CLL) and cases that progress more slowly and are of less immediate concern. The researchers, whose work appears this week in the Proceedings of the National Academy of Sciences, also found that enzyme PDE7B is vital to the development of CLL.
     
    “We found that individuals with high levels really had worse disease, and showed that PDE7B expression had predictive value relative to other currently available markers for disease severity and progression,” said Paul A. Insel, M.D., professor of pharmacology and medicine at the UC San Diego School of Medicine. “In some cases, the level of PDE7B expression provided prognostic information that was additive to existing markers.”

    Previously, the team had discovered that among the cyclic nucleotide phosphodiesterase group of enzymes, PDE7B was 10 times higher in CLL patients than in healthy individuals. PDE7B controls the levels of cyclic AMP (cAMP), a molecule that can promote programmed cell death, a process that is defective in CLL.

    So the question became whether the level of PDE7B expression could provide evidence for the clinical stage and diagnosis for individual patients. To find out if changes in PDE7B levels might reflect disease progression, the group compared the amount of PDE7B in white blood cells in 85 untreated patients with CLL to those of 30 healthy adults, and watched for changes over time. They, then, divided the results into patients who had high levels of PDE7B and those who had low amounts.

    The research suggests that PDE7B has a role in prognosis and also reflects part of the biology of the disease. “The more of this enzyme a patient has, the worse the outcome,” says Dr. Insel. But postodoctoral fellow Linghzi Zhang, Ph.D., acknowledges that PDE7B may need to be teamed with other markers if the level is lower and ambiguous. “PDE7B may not be good enough by itself, if it’s not high enough.”



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