Researchers discover a stem-cell switch lurking within...( Researchers have discovered that specif...)

Researchers have discovered that specific cancer-causing genes associated with leukemias can transform mature white blood cells into leukemic cells that have all the properties of stem cells. The findings are noteworthy because they show that certain leukemia oncogenes can commandeer and switch on genetic programs that govern self-renewal, one of the unique characteristics of stem cells.

The findings may also help explain why the cancer drug Gleevec, which targets the BCR-ABL enzyme, does not cure the disease, but only puts it into remission. The researchers propose that targeting the additional aberrant growth pathway -- outlined in their new studies -- will be necessary to cure chronic myeloid leukemia.

The researchers, led by Gary Gilliland, a Howard Hughes Medical Institute investigator at Brigham and Women's Hospital and Harvard Medical School, published their findings in the December 2004 issue of the journal Cancer Cell. Other co-authors were from the Dana-Farber Cancer Center and Emory University.

Mature white blood cells follow a developmental program that leads to what is called a terminally differentiated state. At that point in development, mature white blood cells have irrevocably lost one of the key properties of stem cells the ability to self-renew indefinitely. "The results of our study are quite surprising, because it had been thought that once a cell was committed to differentiation, it had forever lost the ability to self-renew," said Gilliland. "Our data show that certain leukemia oncogenes can commandeer programs that govern self-renewal and turn the switch back on again."

One of the implications of the study is that it provides new information for researchers to target the cancer stem cell therapeutically. "The cancer stem cell is likely the most important target of therapy," said Gilliland. "It's thought to be the main reason why can
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
21-Dec-2004

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