We propose that as glutamine can be utilized via IDH1-driven reductive carboxylation53, in IDH1 WT AML, flexibility of glutamine utilization provides an adaptive survival mechanism when complex I and the TCA cycle are impaired or inhibited; this promotes mitochondrial citrate usage for the non-canonical pathway for aspartate (via citrate synthase) to support nucleotide synthesis and NADPH maintenance (Fig. 4f)15,54–56. This evidence concerns the gene IDH1 and acute myeloid leukemia.