New Genetic Signature for Leukemia

Leukemia stem cells newly identified produce potential CRG target

(RxWiki News) So what’s a genetic signature you ask? Basically it’s a set of genes in a cell that are involved in how disease starts, grows and spreads. This is hugely complicated and exciting science.

Why? Because it’s giving scientists new insights into how and why disease happens.

Researchers have pinpointed a gene that's behind the development of leukemia stem cells. The new gene signature formed by this gene may help to identify existing drugs to treat leukemia.

Two drugs have been identified as possibilities to target this new set of genes. The drugs are currently being tested, and it will be years before they may prove useful in treating leukemia.

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This work is under way at the University of Rochester Medical Center.

“The research not only provides a better understanding of the basic biology of leukemia – it uncovered genes not previously known to be associated with the disease -- but demonstrates a powerful strategy for drug discovery, said senior investigator, Craig T. Jordan, PhD, the Philip and Marilyn Wehrheim professor of Medicine at URMC and the James P. Wilmot Cancer Center.

Leukemia stem cells aren’t like regular cells. They grow wildly, and they are thought to be the starter cells for cancer.

Other investigators in this study included biomedical genetic researchers, Hartmut (Hucky) Land, PhD and Helene McMurray, PhD. Several years ago Dr. Land’s lab discovered a group of some 100 genes that work together to form colon cancer.

The team named these genes “cooperation response genes” or CRG – another term for gene signature.

CRGs make up a tightly controlled network of soldiers that work together in the cancer march. If these CRGs are turned on, cancer grows. If they’re turned off, the cancer doesn’t progress, according to Dr. Land’s research.

Now leukemia is a cancer of the blood that is really touch to get rid of completely. That’s because most of the standard therapies don’t target and kill the stem cells so that left-over cancer cells circulate in the blood stream.

Once Dr. Jordan’s group identified the new gene signature, researchers used an advanced tool called the Broad Institute’s Connectivity May, which match existing drugs to various genetic signatures.

“We were able to use the latest technology to expand very strong basic laboratory concepts and conduct an intriguing analysis that may yield new insights for treatments of leukemia,” Dr. Jordan said.

“No one else has used the targeting of CRGs as criteria to look for drugs that might treat cancer,” Jordan said.

“By using the CRG approach, we found drug compounds that might never have been selected, based on their documented mechanism of action.”

Findings from this study appeared in the August issue of Cell Stem Cell.

This research was funded by the National Institutes of Health, New York State Stem Cell Foundation, Department of Defense, and a UR Hematology/Oncology training grant.

Review Date: 
August 30, 2012