Cancer Fighting Enzyme May Cause Rare Form Of Leukemia

Armen Hareyan's picture
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An enzyme which has long been known for its ability to fight cancer is now found to cause a rare type of blood cancer.

A team of researchers from Stanford University in California looked at the enzyme named glycogen synthase kinase (GSK3). It is known as an enzyme stopping defective cell growth in numerous types of cancer. The finding surprisingly reports that blocking GSK3 may stop mixed-lineage leukemia (MLL).

"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.

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MLL is a rare type of leukemia which occurs because of MLL gene mutation. This type of blood cancer occurs in 5-10% leukemia sufferers and in 1/3 of infants. Mixed-lineage leukemia mainly affects infants, although it is not yet known why. Leukemia usually starts in lymph nodes or bone marrow, while MLL may occur in both simultaneously. It is quite different than the common form of leukemia and chemotherapy usually doesn't work for it. This is why a better treatment for MLL is needed.

Researchers examined MLL mice who were given MLL lithium - a GSK3 inhibitor, which is mainly used for bipolar disorder treatment. The mice showed to have GSK3 enzyme blocked and lived longer and better than the ones who did not receive any GSK3 inhibitor.

"Most current cancer drugs target both the normal and the aberrant cells," Cleary said. It would be a big advantage in cancer treatment if a drug were developed that could selectively kill cancer but help healthy cells grow. Of course, the danger with GSK3 inhibitors would be that they might also cause other cancers if given long-term. Cleary said it's too early to tell if or how a new drug might skirt that problem.

"There will be a lot of hard work required to get better anti-GSK3 compounds, test them in preclinical models and translate them to human trials," he said.

There are several GSK3 inhibitors in the market for diabetes and Alzheimer's disease treatment, but for mixed-lineage leukemia a better drug needs to be developed.

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