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Leukemia cells evade immune system by mimicking normal cells, Stanford studies show
Date:7/23/2009

killing instinct and allows the marauding cancer cells to escape unscathed.

The current research sprang from an earlier study in Weissman's lab that showed CD47 expression was expressed at significantly higher levels in mouse leukemia cells. "At the time, we didn't know what role CD47 played in leukemia," said Siddhartha Jaiswal, an MD and PhD student at the medical school who is the first author of the second study. "But it was clearly important."

It all fell into place, according to Weissman, when another group showed that red blood cells expressing CD47 were bypassed by macrophages, but those without CD47 were eaten. "Our discovery that leukemia cells in mice also expressed CD47 led us to propose that this signal might be appropriated by the leukemia stem cells as part of their leukemic progression," said Weissman.

Jaiswal and his colleagues went on to show that although rapidly proliferating myeloid leukemia cells in human patients expressed about twice as much CD47 as their normal counterparts, CD47 levels were also temporarily elevated in healthy bone marrow stem cells migrating to organs like the spleen or the liver in response to infection or inflammation, or to bone marrow sites to replenish missing stem cells. A closer look determined why.

"These cells have to cross fields of macrophages guarding these tissues," said Jaiswal. "Because the macrophages are also activated by the same stimuli, these elevated levels of CD47 protect the blood stem cells during this process."

The macrophages' destructive power is exemplified by the fact that mouse bone marrow stem cells lacking CD47 and thus vulnerable to engulfment by the macrophages are unable to rescue mice whose own immune systems have been destroyed. Conversely, a human myeloid leukemia line that normally expresses low levels of CD47 was able to cause leukemia in mice only after Jaiswal engineered it to express higher levels of the molecule. What's more, whe
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Contact: Ruthann Richter
richter1@stanford.edu
650-725-8047
Stanford University Medical Center
Source:Eurekalert

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