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Targeting mitochondrial translation as a novel therapeutic strategy for AML

Aaron David Schimmer

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Canadian Institutes of Health Research (CIHR)
AML (acute myeloid leukemia) is a disease with a poor outcome for which new therapeutic agents are needed. To identify new treatment strategies for AML, we screened a large chemical library of old drugs and identified tigecycline, a drug used for treatment of serious infections that has unrecognized anti-leukemia activity. We demonstrated that tigecycline killed leukemia cells and filed patents claiming the new use of this drug for the treatment of leukemia. Recently this technology was licenses to the Canadian company Stem Cell Therapeutics. Here, we will conduct additional experiments to understand the unique mitochondrial biology in AML and determine the mechanism by which tigecycline kills leukemia cells. Specifically, we will focus on the effects of producing building blocks for RNA and DNA. We will also develop a new test to determine whether tigecycline can hit its miotochondrial target when administered to patients. Finally, in collaboration with Stem Cell Therapeutics, we will synthesize and test novel inhibitors of mitochondrial translation.

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