They found that high levels of a particular enzyme in the blood are an indicator that chronic lymphocytic leukemia (CLL) – the most common form of adult leukemia – will be aggressive and in need of immediate treatment.
The researchers, led by Paul A. Insel, MD, professor of pharmacology and medicine at the UC San Diego School of Medicine, say that the enzyme, PDE7B, is also critical to the development of CLL and a potential target for drugs against the disease. They present their results April 19, 2009 at the AACR 100th Annual Meeting 2009 in Denver.
One of the problems in deciding on the right therapy for CLL is that it is difficult to know which type of leukemia a patient has. One form progresses slowly, with few symptoms for years while the other form is more aggressive and dangerous. While tests exist and are commonly used to help doctors predict which form a patient may have, their availability and usefulness are limited.
In previous work, Insel's group had discovered that among a group of enzymes, cyclic nucleotide phosphodiesterases, one of the phosphodiesterases, 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. 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. 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?" Insel said. To find out if changes in PDE7B levels might reflect disease progression, Insel, postodoctoral fellow Linghzi Zhang, PhD, and their co-workers 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.
"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," Insel said. "In some cases, the level of PDE7B expression provided prognostic information that was additive to existing markers."
Zhang said that PDE7B can be used alone as a biomarker for CLL if the levels are high enough, but may be used with other markers if the level is lower and ambiguous. "PDE7B may not be good enough by itself if it's not high enough," she noted. "If it is low, other markers could be helpful."
Co-investigator and leukemia expert Thomas Kipps, MD, PhD, professor of medicine and deputy director for research at the Moores UCSD Cancer Center, said that the 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.
Insel said that their 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," he said. "This implies that if we can develop drugs to block this enzyme, which would raise cAMP and promote apoptosis – which is really at the heart of the underlying pathology."
The American Cancer Society estimated that in 2008, about 15,100 new cases of CLL occurred in the United States, with roughly 4,400 deaths from the disease.
Other UCSD authors include: Laura Rassenti, Minya Pu, Fiona Murray, Joan Kanter, Andrew Greaves and Karen Messer.
The Moores UCSD Cancer Center is one of the nation's 41 National Cancer Institute-designated Comprehensive Cancer Centers, combining research, clinical care and community outreach to advance the prevention, treatment and cure of cancer.
The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences
Transforming plant cells from generalists to specialists
07.12.2016 | Duke University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine