Leukemia is a cancer of the body's blood-forming tissues, including bone marrow (Acute myeloid leukemia-AML) and the lymphatic system (Acute lymphatic leukemia-ALL). Whereas the lymphatic type has a prevalence in children (80%) with mostly good prognosis, lymphatic leukemia in adults has limited therapeutic options, with poor treatment response and high rate of treatment failure due to chemoresistance. From a metabolic perspective, acquired chemoresistance is associated with a shift toward an OXPHOS-dependent, high-energy status. Since OXPHOS is a key metabolic process that leukemia cells use to maintain high-energy demand, we hypothesized that leukemias with high OXPHOS activity would be responsive to therapeutic inhibition of OXPHOS via Complex I Inhibitor, with particular emphasis on T-ALL leukemias. In this study, we used the Seahorse XF Mito Stress Test and Glycolysis Stress Test to characterize the cellular and metabolic responses to OXPHOS inhibition, and we propose Seahorse Technology as a screening and monitoring tool to control therapeutic response in vivo. Finally, using Mass Spectrometry and confirmed by Seahorse Assays, we identified other metabolic vulnerabilities that can be targeted to overcome acquired resistance to OXPHOS inhibition.
In this webinar we will discuss:
- How the Mito Stress Test and Glycolysis stress test assay can be used for drug screening
- How to identify novel targetable metabolic vulnerabilities
- Use of Mito Stress Test to confirm the findings in vivo