Interactive gene 'networks' may predict if leukemia is aggressive or slow-growing

Dec 08, 2008

Rather than testing for individual marker genes or proteins, researchers at the University of California, San Diego (UC San Diego) and the Moores UCSD Cancer Center have evidence that groups, or networks, of interactive genes may be more reliable in determining the likelihood that a form of leukemia is fast-moving or slow-growing.

One of the problems in deciding on the right therapy for chronic lymphocytic leukemia (CLL) is that it is difficult to know which type a patient has. One form progresses slowly, with few symptoms for years. The other form is more aggressive and dangerous. While tests exist and are commonly used to help predict which form a patient may have, their usefulness is limited.

Han-Yu Chuang, a Ph.D. candidate in bioinformatics and systems biology program in the department of bioengineering in the UC San Diego Jacobs School of Engineering, senior author Thomas Kipps, M.D., Ph.D., professor of medicine and deputy director for research at the Moores UCSD Cancer Center, and their colleagues analyzed the activity and patterns of gene expression in cancer cells from 126 patients with aggressive or slow-growing CLL. The researchers, using complex algorithms, matched these gene activity profiles with a huge database of 50,000 known protein complexes and signaling pathways among nearly 10,000 genes/proteins, searching for "subnetworks" of aggregate gene expression patterns that separated groups of patients. They found 30 such gene subnetworks that, they say, were better in predicting whether a disease is aggressive or slow-growing than current techniques based on gene expression alone.

They presented their results Monday, December 8, 2008 at the annual meeting of the American Society of Hematology in San Francisco.

"We wanted to integrate the gene expression from the disease and a large network of human protein interactions to reconstruct the pathways involved in disease progression," Chuang explained. "By introducing the relevant pathway information, we can do a better job in prognosis." Chuang, co-author Trey Ideker, Ph.D., professor of bioengineering at UCSD, and their co-workers have previously shown the potential of this method in predicting breast cancer metastasis risk.

"When you are analyzing just the gene expression, you are analyzing it in isolation," Chuang explained. "Genes act in concert and are functionally linked together. We have suggested that it makes more sense to analyze the genes' expression in a more mechanistic view, based on information about genes acting together in a particular pathway. We are looking for new markers – no longer individual genes – but a set of co-functional, interconnected genes," she said. "We would like to be able to model treatment-free survival."

The current work is "proof of principle," Chuang said. Clinical trials will be needed to validate whether specific subnetworks of genes can actually predict disease CLL progression in patients. She thinks that the subnetworks can be used to provide "small scale biological models of disease progression," enabling researchers to better understand the process.

Eventually, she said, a diagnostic chip might be designed to test blood samples for such genetic subnetworks that indicate the likely course of disease. The involved biological pathways could be drug targets as well.

The American Cancer Society estimates that, in 2008, there will be about 15,110 new cases of CLL in the United States, with about 4,390 deaths from the disease.

Source: University of California - San Diego

Explore further: Survival hope for melanoma patients thanks to new vaccine

add to favorites email to friend print save as pdf

Related Stories

Gene removal could have implications beyond plant science

23 hours ago

(Phys.org) —For thousands of years humans have been tinkering with plant genetics, even when they didn't realize that is what they were doing, in an effort to make stronger, healthier crops that endured climates better, ...

Diverse gene pool critical for tigers' survival

22 hours ago

(Phys.org) —New research by Stanford scholars shows that increasing genetic diversity among the 3,000 or so tigers left on the planet is the key to their survival as a species.

Aging research goes to the dogs

Apr 15, 2014

From ancient alchemical quests to modern biological research, efforts to understand and combat human aging have borne few fruits. Now Cornell scientists aim to bridge the gap between lab research and aging's ...

Recommended for you

Survival hope for melanoma patients thanks to new vaccine

31 minutes ago

(Medical Xpress)—University of Adelaide researchers have discovered that a new trial vaccine offers the most promising treatment to date for melanoma that has spread, with increased patient survival rates and improved ability ...

New clinical trial launched for advance lung cancer

4 hours ago

Cancer Research UK is partnering with pharmaceutical companies AstraZeneca and Pfizer to create a pioneering clinical trial for patients with advanced lung cancer – marking a new era of research into personalised medicines ...

User comments : 0

More news stories

Firm targets 3D printing synthetic tissues, organs

(Medical Xpress)—A University of Oxford spin-out, OxSyBio, will develop 3D printing techniques to produce tissue-like synthetic materials for wound healing and drug delivery. In the longer term the company ...

Survival hope for melanoma patients thanks to new vaccine

(Medical Xpress)—University of Adelaide researchers have discovered that a new trial vaccine offers the most promising treatment to date for melanoma that has spread, with increased patient survival rates and improved ability ...

New clinical trial launched for advance lung cancer

Cancer Research UK is partnering with pharmaceutical companies AstraZeneca and Pfizer to create a pioneering clinical trial for patients with advanced lung cancer – marking a new era of research into personalised medicines ...

Biologists help solve fungi mysteries

(Phys.org) —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Robotics goes micro-scale

(Phys.org) —The development of light-driven 'micro-robots' that can autonomously investigate and manipulate the nano-scale environment in a microscope comes a step closer, thanks to new research from the ...