Boston, Mass. About 40 percent of children and up to 70 percent of adults in remission from acute myelogenous leukemia (AML) will have a relapse. In recent years, doctors have come to believe that this is due to leukemia stem cells, endlessly replicating cancer cells that generate the immature blood cells characteristic of leukemia and are resistant to typical cancer treatments. Now, researchers at Children's Hospital Boston have found a possible way to kill off these cells, and prevent them from initiating a relapse.
The study, published online March 26th in the journal Science, shows that leukemia stem cells cannot thrive without a particular cell pathway, known as the Wnt/beta-catenin pathway, suggesting that targeting this pathway may prevent the growth and development of AML.
"The biggest potential for this study is in suppression of leukemia recurrence by a drug that inhibits beta-catenin," says Scott Armstrong, MD, PhD, of Children's Division of Pediatric Hematology/Oncology and senior author of the study.
Yingzi Wang, PhD, of Children's Division of Pediatric Hematology/Oncology, a member of Armstrong's team and lead author of the study, zeroed in on beta-catenin as an important player in leukemia stem cells by working with two different types of early blood cells blood stem cells, which generate all the different types of blood cells, and granulocyte/macrophage-restricted progenitors, more mature, differentiated cells that only generate certain white blood cells. They did this by activating two genes previously found to induce AML, Hoxa9 and Meis1, then injecting the cells into mice.
Activation of the two genes induced AML in mice injected with the blood stem cells, but not in mice injected with the progenitors. Genetic analyses revealed the progenitors lacked an active beta-catenin pathway. Though this pathway is still active in blood stem cells after a person is born, it plays a vital role only during fet
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Children's Hospital Boston