Figure 1.

Overview of the central metabolic pathways of leukemic blasts (A), leukemic stem cells (B), and activated T cells (C). (A) Leukemic blasts import glucose via the glucose transporter GLUT1 (50). The ingested glucose is metabolized to pyruvate in the process of glycolysis and subsequently fermented to lactate (51). Additionally, leukemic cells import fructose via GLUT5 under low extracellular glucose levels (52). Fatty acids are oxidized to acetyl-CoA, which enters the TCA cycle (53). Glutamine, imported via glutamine transporter SLC1A5, is converted into the TCA cycle intermediate α-ketoglutarate in the process of glutaminolysis (54). Other amino acids, especially arginine and cysteine, are increasingly imported from the extracellular space (55, 56). (B) Leukemic stem cells predominantly use OXPHOS for ATP production (57). The TCA cycle is fueled by the oxidation of fatty acids (58, 59). Moreover, LSCs import cysteine, which is used for glutathione synthesis (60). (C) Activated CD8⁺ T cells use aerobic glycolysis as the main energy source (61). Fatty acid synthesis is upregulated resulting in an accumulation of fatty acid metabolites needed for membrane synthesis (62). Furthermore, T cells increase the uptake of glutamine, which, converted to α-ketoglutarate, is used to replenish the TCA cycle (63). GLUT1, glucose transporter 1; GLUT5, glucose transporter 5 (mediates fructose uptake); ATP, adenosine triphosphate; CoA, coenzyme A; TCA, tricarboxylic acid; α-KG, α-ketoglutarate; OXPHOS, oxidative phosphorylation; SLC1A5, solute carrier family 1 (neutral amino acid transporter) member 5.