GLS and acute myeloid leukemia: Glutamine is the main source of α-KG in IDH-mutated leukemia cells, leading to a glutamine dependence.193,206 Targeting this metabolic dependence through inhibition of glutamine metabolism has been shown to suppress growth of IDH-mutated AML cells.206,207 CB-839 is an orally bioavailable glutaminase inhibitor that has been demonstrated to reduce levels of 2-HG in IDH-mutated AML cells, ultimately promoting the differentiation of leukemic cells (Fig. 4).