Dual dietary and pharmacological targeting of OxPhos in T-ALL
Mentor Name: Daniel Herranz
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive, hematologic malignancy that occurs primarily in children. Despite recent clinical advances, 20-50% of patients show primary resistance or relapse after treatment. T-ALL is amenable to metabolic interventions as well as amino-acid deficient diets, aspartate-deficient diets in particular. The process of mitochondrial oxidative phosphorylation (OxPhos) has a primary role of enabling aspartate synthesis; thus we hypothesize that targeting OxPhos while concomitantly using aspartate-deficient diets would lead to highly synergistic antileukemic effects. To test this hypothesis, we will treat leukemic mice with aspartate-deficient diets, the OxPhos-targetting drug metformin, or a combination of both. If strong antileukemic effects are observed, we will pursue mechanistic studies both in vitro and in vivo further down the road.
