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AMKL accounts for about 10 percent of pediatric AML.
James Downing, MD, St. Jude scientific director and the Pediatric Cancer Genome Project’s St. Jude leader, was senior scientist in a study that found almost 30 percent of patients with this subtype of leukemia have cancer cells that produce an abnormal protein.
Investigators linked the protein to the rearrangement of chromosome 16. The rearrangement brings together the front end of a gene for making a blood protein and the back end of a gene not previously linked to cancer. That gene makes a protein normally produced only in kidney cells. The result is called a fusion protein.
When researchers introduced the fusion protein into a variety of laboratory models, the protein switched on genes that drive immature blood cells to keep dividing long after normal cells have died. Such unchecked cell division is a hallmark of cancer.
Not only does the fusion gene contribute directly to cancer development, but researchers found that patients with the mistake were more likely to fail therapy.
Now St. Jude investigators are beginning the task of translating these discoveries into treatments for patients.
“We are collaborating with the Department of Chemical Biology and Therapeutics to identify compounds that are effective against this leukemia subtype,” says Tanja Gruber, MD, PhD, a St. Jude oncologist who helped lead the AMKL study.
Abridged from Promise, Spring 2013