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Figure 2. Genotype-metabolism-therapy axis in AML. Mechanistic diagram linking key genetic/epigenetic drivers (IDH1/2, EZH2/BCOR/SETD2 loss, KMT2A-r/FLT3-ITD/NUP98::KDM5A, TP53-mutant OxPhos-high LSCs) to metabolic hallmarks (2-HG production, serine/glycine/one-carbon flux via PHGDH/PSAT1/SHMT2, pyrimidine synthesis via DHODH, cystine uptake via SLC7A11). Targeted therapies and biomarkers include IDH inhibitors (ivosidenib/enasidenib) with 2-HG monitoring, venetoclax/azacitidine for OxPhos LSCs, PHGDH/DHODH inhibition, and SLC7A11/cyst(e)inase-mediated ferroptosis induction Figure generated using AI-based tools and finalized by the authors in Microsoft PowerPoint. AML: Acute myeloid leukemia; TCA: tricarboxylic acid; PHGDH phosphoglycerate dehydrogenase; PSAT1: phosphoserine aminotransferase; SHMT2: serine hydroxymethyltransferase 2; DHODH: dihydroorotate dehydrogenase; ADA: adenosine deaminase; IDH: isocitrate dehydrogenase; AI: artificial intelligence; DHODH: dihydroorotate dehydrogenase.