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New biomarker can predict disease aggressiveness

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Published: 04/24/09
CLL in a skin biopsy
CLL in a skin biopsy

Denver—Scientists have evidence of a potential new biomarker to predict the aggressiveness of chronic lymphocytic leukemia (CLL).
The researchers, led by Paul A. Insel, MD, of University of California San Diego School of Medicine, say the enzyme, PDE7B, is also critical to the development of CLL and a potential target for drugs against the disease. They presented their results at the AACR 100th Annual Meeting, which took place April 18-22.

In previous work, Dr Insel's group had discovered that PDE7B was 10 times higher in CLL patients than in healthy individuals. PDE7B controls the levels of cyclic AMP (cAMP), which can promote programmed cell death. High levels of PDE7B mean less cAMP and as a result, less cell death.

"The question was, could the level of PDE7B expression provide evidence for the clinical stage and diagnosis for individual patients?" Dr Insel said.

To find out if changes in PDE7B levels might reflect disease progression, Dr Insel and colleagues 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. The team then divided the results into patients who had high levels of PDE7B and those who had low amounts.

"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," Dr Insel said. "In some cases, the level of PDE7B expression provided prognostic information that was additive to existing markers."

PDE7B can be used alone as a biomarker for CLL if the levels are high enough, but it may be used with other markers if the level is lower and ambiguous.

The researchers said these findings are potentially important because of the urgency for clinicians to be able to gauge early on what kind of disease the CLL patient has in order to design the best available therapy. The team’s research to date implies that PDE7B has a role in prognosis and could also be a good drug target because it reflects part of the biology of the disease.

"The more of this enzyme a patient has, the worse the outcome," Dr Insel said. "This implies that, if we can develop drugs to block this enzyme, [it] would raise cAMP and promote apoptosis, which is really at the heart of the underlying pathology."


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