Targeting Metabolic Reprogramming in Acute Myeloid Leukemia

Abstract

The cancer metabolic reprogramming allows the maintenance of tumor proliferation, expansion and survival by altering key bioenergetics, biosynthetic and redox functions to meet the higher demands of tumor cells. In addition, several metabolites are also needed to perform signaling functions that further promote tumor growth and progression. These metabolic alterations have been exploited in different cancers, including acute myeloid leukemia, as novel therapeutic strategies both in preclinical models and clinical trials. Here, we review the complexity of acute myeloid leukemia (AML) metabolism and discuss how therapies targeting different aspects of cellular metabolism have demonstrated efficacy and how they provide a therapeutic window that should be explored to target the metabolic requirements of AML cells.

Keywords: acute myeloid leukemia; metabolism; preclinical and clinical trials on metabolic targets.

Figure 1

Overview of an acute myeloid leukemia cell’s metabolism. Metabolic reprogramming provides ATP and intermediates for the synthesis of nucleotides, amino acids, lipids and redox elements (NADPH) needed to sustain high proliferation rates. Further details are found in the main body of text. PPP—pentose phosphate pathway; IDH1,2/3—Isocitrate dehydrogenase 1,2/3; GLS—glutaminase; GLUD—glutamate dehydrogenase; GLUTs—glucose transporters; MCTs—monocarboxylate transporters; OXPHOS—Oxidative Phosphorylation.