Molecule Helps Leukemia Cells Hide From Immune System
THURSDAY, July 23 -- Leukemia stem cells cleverly cloak themselves to avoid detection by a person's immune system, according to a pair of studies by researchers at Stanford University Medical School.
The cells co-opt a protective molecular badge that is used by normal blood stem cells, and this badge helps them travel throughout the body undetected, the investigators found.
Patients who had cancer stem cells with higher levels of this molecule have a poorer prognosis than those whose cells express lower levels, the researchers report in the July 24 issue of the journal Cell.
"We call it the 'Don't eat me signal,'" said Dr. Ravindra Majeti, assistant professor of hematology at Stanford, co-first author of the studies, which focused on acute myeloid leukemia.
"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 in a news release from Stanford.
The study findings show that the molecule could be a prognostic factor and a valuable therapeutic target for treatment of the malignancy.
The researchers found that the molecule, CD47, protects the leukemia stem cells from macrophages by binding to a molecule on the macrophage's surface. The macrophages are part of a group of cells that travel around in an effort to find and engulf diseased or dying cells. The interaction between the two proteins gets in the way of the macrophage's instinct to kill and allows the cancer cells to escape.
In the study, the high-CD47-expressing cancer stem cells were put in a culture dish with an antibody that blocks the interaction of the cancer cells with macrophages, essentially hiding the protective badge. This allowed the macrophages to "see" and engulf the cancer cells. In the study in mice, a similar treatment prevented human cancer cells from causing leukemia in the animals, and even helped mice that already had leukemia to survive longer.
"This was the real kicker," Majeti said. "These mice showed a profound clinical response."
The next step for the researchers is to go forward with plans to test a similar treatment in humans.
Posted: July 2009
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