STANFORD, Calif. Human leukemia stem cells escape detection by co-opting a protective molecular badge used by normal blood stem cells to migrate safely within the body, according to a pair of studies by researchers at Stanford University Medical School.
"We call it the 'Don't eat me signal,'" said Ravindra Majeti, MD, PhD, assistant professor of hematology at the medical school and the co-first author of one of the studies, which focused on acute myeloid leukemia.
Patients whose cancer stem cells express higher levels of the molecule have a poorer prognosis than those whose cells express lower levels, and masking its presence makes the human cancer cells less deadly and more vulnerable to destruction when injected into mice. The results indicate that the molecule may serve both as a prognostic factor and a valuable therapeutic target for patients with the cancer.
"When we blocked this signal in mice with established human leukemia, the cancer cells were more easily removed by the body's natural defenses," Majeti said. The researchers are now moving ahead with plans to test a similar treatment in humans and have filed for a patent for the potential therapy.
Irving Weissman, MD, the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research at the medical school, is the senior author of both studies, which will be published together in the July 24 issue of the journal Cell. Majeti shares his first authorship with Mark Chao, an MD and PhD student in the cancer biology program at the medical school. Both Majeti and Weissman are members of Stanford's Cancer Center.
Together, the researchers of the studies found that the molecule, CD47, protects the leukemia stem cells from macrophages part of a roving cellular army tasked with finding and engulfing diseased or dying cells by binding to a molecule on the macrophage's surface. The interaction between the two proteins inhibits the macrophage's
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Stanford University Medical Center