Mutation Promotes Survival of Leukemia Stem Cells

Cancer researchers have pinpointed a genetic error that permits cancerous stem cells to survive chemotherapy and reestablish the disease.

Investigators from the University of Texas Health Science Center (San Antonio, USA) and colleagues from other institutions studied chronic myeloid leukemia (CML) as a representative of a broad range of cancerous diseases. Using advanced gene mapping techniques and working with CML tumor cells and stem cells transplanted into immunocompromised mice, the investigators found a mutation resulting from a novel in-frame splice deletion of the GSK3-beta kinase domain. This change in the CML's stem cell DNA, an abnormality in the Wnt/beta catenin self-renewal pathway, gave the malignant cells an advantage over normal stem cells in terms of growth and survival.

"We believe stem cells are the obstacle to a cure for leukemia,” said contributing author Dr. Francis Giles, professor of hematology and medical oncology at the University of Texas Health Science Center. "If we have killed nearly all of a patient's cancer cells, but we have not killed the stem cells, we have not cured the patient. A marker helps us find the elusive stem cells, quantify them, and follow their behavior in patients. Then we can see how the stem cell behavior differs from that of other more mature cancer cells, and develop stem cell-directed new therapies. Perhaps we can tell the stem cells to ignore their previous instructions and get them to change into another type of cancer cell that we know how to kill.”

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University of Texas Health Science Center