HIF1A and acute myeloid leukemia: In primary human AML blasts, both TIM-3-agonistic antibody and Gal-9 (as the natural TIM-3 ligand) significantly upregulated the mTOR pathway, enhancing the accumulation of pro-tumoral factors including hypoxia-inducible factor 1 alpha (HIF-1α) and the secretion of VEGF and TNF-α [97].