Highly Expressed Surface Marker Protects Leukemia Cells

Leukemia cells that overexpress the cell surface marker CD47 are protected from macrophage destruction, and acute myeloid leukemia (AML) patients with this situation have a poor prognosis.

Investigators from Stanford University (Stanford, CA; USA) published two articles on the role of CD47 in AML in the July 24, 2009, issue of the journal Cell. They reported that cell-surface CD47 interacts with its receptor on macrophages, SIRP-alpha, to inhibit phagocytosis of normal, healthy cells. In particular, CD47 expression was found on migrating blood-forming cells that had to pass through fields of macrophages while moving from the bone marrow into the circulation. In a similar fashion, CD47 on a myeloid leukemia line increased its pathogenicity by allowing it to evade phagocytosis.

The investigators blocked CD47 with a specific monoclonal antibody. This treatment caused leukemia cells to be taken up and destroyed by immune macrophages. In a mouse model of human leukemia, treatment with monoclonal anti-CD47 cleared the disease and enabled the animals to survive.

"AML is treated today with high dose chemotherapy and in many cases bone marrow transplants,” said contributing author Dr. Ravindra Majeti, professor of clinical hematology at Stanford University. "The truth is that the overall survival is really dismal, with 30% to 40% of patients surviving at five years. The situation for those over the age of 65 can be much worse, and the disease is one that principally affects the elderly. There is therefore an urgent need to develop novel therapeutic agents with less toxicity, and the antibody therapy might fit the bill.”

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