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Researchers discover how a mutated protein outwits evolution and fuels leukemia
Date:6/20/2013

Scientists have discovered the survival secret to a genetic mutation that stokes leukemia cells, solving an evolutionary riddle and paving the way to a highly targeted therapy for leukemia. In a paper published today in Cell, researchers at NYU Langone Medical Center describe how a mutated protein, called Fbxw7, behaves differently when expressed in cancer cells versus healthy cells. "Fbxw7 is essential for making blood cells, so the big mystery is why a mutation on a gene so important for survival would persist," says lead author Iannis Aifantis, PhD, chair of pathology at NYU Langone Medical Center and an Early Career Scientist at Howard Hughes Medical Institute. "What we've found is that the mutation affects cancerous cells but not healthy cells."

The Fbxw7 protein regulates the production of so-called hematopoietic stem cells, precursors that give rise to all types of blood cells. Without Fbxw7, the body loses the ability to produce blood and eventually succumbs to anemia. Scientists are only beginning to understand why mutated Fbxw7 appears in a significant portion of human tumors, including gastric, prostate, and some breast cancers. The mutation is especially prevalent in T-cell acute lymphoblastic leukemia, or T-ALL, a rare but lethal type of pediatric leukemia that causes the over-production of immature white blood cells.

In their experiments, Dr. Aifantis, working in collaboration with graduate student Bryan King and others, began by introducing mutated Fbxw7 into healthy blood stem cells in mice. "We thought the mutation would induce anemia, just as it does when Fbxw7 is deleted," says Dr. Aifantis. But to the researchers' surprise, nothing happenedthe stem cells continued to manufacture blood cells.

When the researchers then introduced in mice the mutated Fbxw7 into leukemic blood stem cellsthose that overproduce white blood cells and cause leukemiathe cancer accelerated. "We found that the mutation made leukemia
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Contact: Christopher Rucas
Christopher.Rucas@nyumc.org
212-404-3525
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

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