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New leukemia signal could point way to better treatment, Stanford researchers find
Date:9/17/2008

STANFORD, Calif. - Cancer researchers at the Stanford University School of Medicine have discovered a promising new chemotherapy target for a deadly form of leukemia. Their discovery hinges on a novel "double agent" role for a molecular signal that regulates cell growth.

The rogue signal, glycogen synthase kinase 3, was previously found to halt uncontrolled cell growth, preventing several forms of cancer. It also keeps growth of healthy cells in check. But new data show that GSK3 fuels a deadly form of white blood cell cancer, which accounts for five to 10 percent of child and adult leukemias and more than three-quarters of leukemias diagnosed in infants.

"This finding was quite unexpected," said Michael Cleary, MD, senior author of a paper describing the discovery. "GSK3 has never been implicated in promoting cancer." Cleary is a professor of pathology and of pediatrics and a member of the Stanford Cancer Center. The research will appear online in Nature on Sept. 17.

Cleary's team discovered that inhibiting GSK3 combats leukemias caused by mutated MLL genes. MLL, an acronym for "mixed-lineage leukemia," refers to an unusual feature of these deadly cancers. Most leukemias begin in just one of the body's two white blood cell factories, either the lymph nodes or the bone marrow. But in mixed-lineage leukemias, the bad cells can show markers from both kinds of tissue.

Newly diagnosed leukemia patients have their cancer cells tested to see which genes are driving the cancer. Mutated MLL genes are viewed as a bad prognostic marker, Cleary said.

"There is intense interest in coming up with better ways to treat these patients," he said. Cleary's findings indicate GSK3 may be an effective target for future leukemia drugs.

The first hint of GSK3's role came from petri-dish tests on cancer cells. Postdoctoral scholar Zhong Wang, PhD, treated dishes of different kinds of cancer cells with a battery of che
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Contact: Erin Digitale
digitale@stanford.edu
650-724-9175
Stanford University Medical Center
Source:Eurekalert

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