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Regulation of Leukemia Stem Cell Activity by Signaling through PKC[theta]

Andrew Weng

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Canadian Institutes of Health Research (CIHR)
T-cell acute lymphoblastic leukemia, or "T-ALL", is a type of blood cancer that affects children and adults worldwide, with approximately 30 new cases per million children and 10 new cases per million adults diagnosed each year. Within Canada, this adds up to about 80 new cancer patients per year in total. While current treatments cure about 80% of children, only about 40% of adults are as fortunate. Even for those who are cured, the chemotherapy they have to go through makes them very sick and can cause other, long-term health problems. Dr. Weng's team has recently shown that a molecule called "protein kinase C theta", or PKCtheta, is a critical regulator of cancer stem cells in T-ALL, which are thought to be responsible for disease relapse even after successful chemotherapy. In this study, Drs. Weng and Morin now propose to use a cutting edge technology called "mass spectrometry" to discover exactly what PKCtheta does in cancer stem cells by identifying what other molecules in the cell it interacts with. The results of this work will form the basis for design of new drugs that target PKCtheta signaling elements in hopes that they will be more effective in curing patients with leukemia than traditional chemotherapy. While the immediate goals of this research are to cure T-ALL, we predict that PKCtheta will activate common cellular pathways that control cancer stem cells more generally, and thus these studies may provide leads towards identifying cures for other cancers as well.

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