Fig. 1

TIM-3/Gal-9 and glutamine metabolism. Gal-9 can be as free form or cell surface ligand on T cells, dendritic cells, and endothelial cells or other cells in the tumor microenvironment. After binding of the Gal-9 ligand to the TIM-3 receptor on the surface of AML leukemic cells through autocrine or paracrine pathways, the PI3K/AKT/mTORC signaling pathway is activated. mTORC is related to (1) the glycolysis pathway, (2) the Krebs cycle (TCA), (3) glutamine metabolism, (4) protein synthesis, and (5) cell proliferation. mTORC can act as an amino acid sensor and after the amino acid glutamine enters into the AML cell, it triggers (3) the pathway of glutamine degradation (glutaminolysis) by the enzymes GLS and GDH which respectively converts Gln to Glu and Glu to α-KG in mitochondria of leukemic blast. The dimensions of the cell components are relative and not real. The figure was Created in BioRender.com. TIM-3: T-cell immunoglobulin and mucin domain 3; Gal-9: Galectin-9; PI3k: phosphatidylinositol 3-kinase; AKT: or Protein kinase B (PKB); mTORC: mammalian target of rapamycin complex; TCA: tricarboxylic acid cycle; GLS: Glutaminase; GDH: Glutamate dehydrogenase; Gln; Glutamine; Glu: Glutamate; α-KG: alpha-ketoglutarate