Microenvironmental cysteine essential for LSCs in AML. (A) Schematic overview of cysteine metabolism. (B) Metabolically defined LSCs purified by fluorescence-activated cell sorting based on low dihydrodichlorofluorescein (DCF) or CellROX staining and with their major identified characteristics. (C) Mitochondrial cysteine metabolism and gluthathionylation of ROS-low LSCs sensitive to or resistant to venetoclax (V) plus azacitidine (A or Aza). Diag, diagnosis; FAO, fatty acid oxidation; GCL, glutamate cysteine ligase; GS, glutathione synthase; homocys, homocysteine; MeTHF, methyl-tetrahydrofolate; OxPHOS, oxidative phosphorylation; THF, tetrahydrofolate; SAHcys, S-adenosyl-homocysteine; SAM, S-adenosyl-methionine.