5th International Conference and Exhibition on Metabolomics
University of Maryland School of Medicine, USA
Title: Interference with glutamine metabolism: a novel approach for treatment of acute myeloid leukemia
Biography: Ashkan Emadi
In contrast to normal cells, rapidly dividing leukemia cells reprogram their nutritional requirements to match an increased metabolic demand. The two main nutrient sources for growth and survival of cancer cells are glucose and glutamine. Depletion of glutamine or interruption of its cellular processes can be detrimental to leukemia cells but not normal cells. Asparaginases deplete amino acids asparagine and glutamine and are FDA-approved drugs for the treatment of acute lymphoblastic leukemia (ALL). The anti-leukemia effect of asparaginases in acute myeloid leukemia (AML) is not established. Here we describe the preclinical effect of different asparaginase products on the survival of AML cells with or without isocitrate dehydrogenase (IDH) mutations, which culminates in glutamine depletion resulting in disruption of protein synthesis downstream of mammalian target of rapamycin (mTOR) causing strong apoptotic and autophagic responses. The clinical experience with asparaginase in AML patients will also be discussed. Moreover, the cytotoxic effect of pharmacologic inhition of glutaminase, the enzyme that converts glutamine to ammonia and glutamate, will be reported in AML cells with different mutational status.