Grant: Project Grant

Acute myeloid leukemia (AML) is a deadly disease with few therapy options. Recent work has shown that leukemia cells are metabolically rewired such that compounds targeting mitochondria are able kill leukemia cells without killing normal cells. Thus, identifying new drugs that target these mitochondria vulnerabilities could improve AML patient outcomes. Mitochondria possess four complexes that are responsible for cell respiration and energy production. In leukemia cells, mitochondria complex II activity is higher than the other complexes. This suggests that targeting and inhibiting complex II might be a simple yet powerful way to selectivity target and kill leukemia cells. Indeed, our preliminary research shows that inhibiting mitochondria complex II selectively kills leukemia cells in vitro and in vivo. In this project, the objective is to further validate, and define how, targeting of this complex imparts selective leukemia cell killing. The end goal of this work is to develop new drugs aimed at extending the lives of leukemia patients.