Mixed-lineage leukemia (MLL) is a rare type of blood cancer which occurs in 5-10 percent of child and adult leukemia sufferers and more than three-quarters of infants diagnosed with leukemia. MLL is quite different than the common form of leukemia in that while most leukemia starts in the lymph nodes or bone marrow, MLL may occur in both simultaneously and usually doesn’t respond well to chemotherapy. However, a surprising discovery may lead to new treatments for this hard-to-treat cancer.
Through routine screening tests in the lab, a team of researchers from Stanford University in California found that blocking a sugar-regulating enzyme helped mice with MLL live significantly longer and better than untreated mice. The enzyme, glycogen synthase kinase 3 (GSK3), was previously found to help suppress cell growth in other cancers. “This finding was quite unexpected. GSK3 has never been implicated in promoting cancer,” study senior author Dr. Michael Cleary, a professor of pathology and of pediatrics, said in a Stanford news release.
To suppress GSK3, the mice were given lithium, which is mainly used in humans for bipolar disorder treatment. “It is not the best GSK3 inhibitor, but it is one that could be administered long-term in mice,” Dr. Cleary said. “I think where we need to go in the future is to come up with better inhibitors that can be administered long-term.” That may come through research of the drug in other diseases. Dr. Cleary said drug companies are developing GSK3 inhibitors as treatments for diabetes and Alzheimer’s disease.
Now that the Stanford team has identified GSK3 as a potential drug target, they are studying how GSK3 actually fuels MLL. “There is intense interest in coming up with better ways to treat these patients,” said Dr. Cleary. “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.”
Dr. Cleary said that since “most current cancer drugs target both the normal and the aberrant cells,” 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. He said it is too early to tell if or how a new drug might circumvent that problem.
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