Fig. 5: Metabolic profile of AML HSPCs.

a, The experimental design to characterize the metabolome and transcriptome of HSPCs (lineage⁻ CD34⁺ CD38⁻) from healthy participants and patients with AML. The input material per sample and number of detected metabolites and genes are indicated. Created with BioRender.com. b, A heat map of all detected metabolites passing quality thresholds in human targeted metabolomics of AML and healthy HSPCs. The log₂FC values between each AML biological replicate and the average of healthy HSPCs are depicted. n = 15–17; 2-HG, 2-hydroxyglutarate. c, PCA of AML HSPC samples normalized to their healthy counterparts based on all detected metabolites. Colour depicts the categorization of patients based on their common mutations. Lines represent two groups based on the amino acids levels compared with healthy participants. d, A volcano plot of transcriptome differentially expressed genes (DEGs) in TET2-mutated AML versus healthy HSPCs. P-adjusted value. n = 3–7. e, GSEA of cellular amino acid metabolic process GO term in TET2-mutated AML versus healthy HSPC RNA-seq. P-adjusted value. f, A heat map representing the relative expression of differentially expressed KEGG enzymes in TET2-mutated AML versus healthy HSPCs (log₂FC threshold of 1, P-adjusted < 0.05), classified in their respective metabolic pathways. In b–d, n indicates the number of biological replicates per condition. For b, 12 independent experiments were performed. PC, principal component.