NOT ALL BAD: Macrophages, such as the one shown in this artificially colored scanning electron micrograph, may help or hinder cancer’s spread.D. PHILLIPS/SCIENCE PHOTO LIBRARYIn the late 2000s, Stanford University stem cell biologist Irving Weissman wanted to understand how normal blood-forming stem cells differed from those that went on to seed a type of blood cancer called acute myelogenous leukemia (AML). Using bone marrow samples from AML patients who had survived the nuclear bombs dropped on Japan during World War II, his team identified the developmental stage at which blood-forming stem cells branch off to become cancerous and compared gene expression profiles between those cells and their counterparts from healthy bone marrow samples. The researchers found that the leukemia-forming stem cells highly expressed a gene encoding CD47, a surface molecule known for its role on normal, healthy cells as a “don’t eat me” signal to phagocytosing macrophages. Weissman and his colleagues had no clue how CD47 had gotten onto cancer cells, but they couldn’t ignore it. “The molecule was just staring us in the face,” he says.
The researchers looked at stem cells from AML patients at the Stanford Medical Center to see if they also expressed CD47. “They all did,” says Weissman. After demonstrating in cell culture experiments that macrophages only engulfed AML cells that did not display CD47 on their surface, Weissman’s team grew human AML cells in five immune-deficient mice and treated the animals with an antibody against CD47.1 In just two weeks, AML cells were nearly undetectable in the animals’ blood, and had dropped by 60 percent in their bone marrow. “It was shocking,” says Weissman, noting that four of the five mice were essentially cured. “We knew that we were on the track of a potential therapeutic.”
In less than a decade, Weissman and his colleagues at ...
