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Stripping leukemia-initiating cells of their 'invisibility cloak'
Date:7/23/2009

Two new studies reveal a way to increase the body's appetite for gobbling up the cancer stem cells responsible for acute myeloid leukemia (AML), a form of cancer with a particularly poor survival rate. The key is targeting a protein on the surface of those cells that sends a "don't eat me" signal to the macrophage immune cells that serve as a first line of defense, according to the reports in the July 24th issue of the journal Cell, a Cell Press publication.

In essence, says Irving Weissman of Stanford University, that signal sent by a cell-surface protein known as CD47 "is an invisibility cloak for leukemia stem cells." Safe from the macrophages whose job it is to clear pathogens and damaged or aging cells from the bloodstream, the CD47-coated leukemia-producing cells are free to traverse the circulation, navigating macrophage-lined blood vessels of the spleen, liver and marrow, and lodging tumors along the way.

The same signal is also temporarily produced at lower levels by normal blood-forming stem cells when they migrate, said Siddhartha Jaiswal, also of Stanford. "CD47 is the vehicle that allows normal stem cells to move from one bone marrow site to another," he explained. To do that, they too must pass a field of macrophages.

"It's something protective on normal cells that's acquired by these malignant cells," Weissman said. The leukemia stem cells co-opt this ability and take it to an extreme in order to evade macrophage killing.

With their colleagues Ravindra Majeti and Mark Chao at Stanford, the researchers further extended their initial findings in mice to humans in the second study. They found that CD47 is more highly expressed on human acute myeloid leukemia stem cells than on their normal stem cell counterparts. Among adult patients with AML, higher CD47 levels predicted worse overall survival, they report.

Antibodies against CD47 allowed the cancer stem cells to be eaten by macrophages and preve
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Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

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