Vitamin metabolism in AML and relevant therapeutic strategies. (A) Regulation of TET enzymes by vitamin C (ascorbate). Schematic representation demonstrating the ascorbate-dependent regulation of the TET enzymes by ascorbate, as well as downstream epigenetic effects in HSCs (multipotent progenitors [MPPs]) and cancer stem cells. (B) Regulation of vitamin B6 (pyridoxal) in AML. Schematic representation of pyridoxal uptake and downstream utilization in AML cells, including a central role for PLP and downstream effector enzymes, ODC1 and GOT2 in leukemic proliferation. Enzymes and inhibitory compounds with demonstrated relevance to AML pathophysiology are highlighted in blue, and red, respectively. BER, base exclusion repair; 5CaC, 5-carboxylcytosine; 5fC, 5-formyl cytosine; DHA, dehydroascorbate; GOT2, glutamic-oxaloacetic transaminase 2; 5mC, 5-methylcytosine; 5hmC, 5-hydroxymethylcytosine; ODC1, ornithine decarboxylase.