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

December 8, 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: Genetic discovery may help better identify children at risk for type 1 diabetes

Related Stories

Genetic discovery may help better identify children at risk for type 1 diabetes

January 17, 2018
Six novel chromosomal regions identified by scientists leading a large, prospective study of children at risk for type 1 diabetes will enable the discovery of more genes that cause the disease and more targets for treating ...

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

Adult leukaemia can be caused by gene implicated in breast cancer and obesity

January 16, 2018
When people think of leukaemia, they usually think of blood cancers that affect children. These mostly come under the category of acute lymphoblastic leukaemia – or ALL – and are different to the group of blood cancers ...

Computer-aided facial analysis helps diagnosis

January 16, 2018
In rare diseases, the computer-aided image analysis of patient portraits can facilitate and significantly improve diagnosis. This is demonstrated by an international team of scientists under the leadership of the University ...

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

0 comments

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.