Fig. 2: Imatinib partially reverses BCR-ABL driven metabolic reprogramming of human CML cells.

a Schematic overview of paired omic dataset generation from human CML cells (n = 4) exposed to imatinib. CD34+ cells were treated in vitro with 2 µM imatinib for 48 h. Created with BioRender.com (Agreement number: UV25IFAAWP). b GSEA conducted on data described in (a) using Hallmark gene sets. The downregulated gene sets are shown. c GSEA conducted using Hallmark gene sets on CML CD34+ cells treated with imatinib for 7 days. The downregulated gene sets are shown. d Imatinib-downregulated gene sets (from (b)), shown are fatty acid oxidation, glycolysis and oxidative phosphorylation. e Imatinib-downregulated gene sets (from (c)), shown is oxidative phosphorylation. f Volcano plot comparing metabolite steady state levels between control and imatinib treated CML CD34+ cells (n = 4 patient-derived samples, 2 independent experiments). Cells were treated with 2 µM imatinib for 48 h. Red coloured metabolites have q value < 0.05 and blue coloured metabolites have a q value < 0.1. Multivariate analysis was carried out using MetaboAnalyst 5.0. The Benjamini-Hochberg FDR method was used to correct for multiple comparisons. g AMP/ATP ratios are shown (n = 4 patient-derived samples). Statistical analysis performed using a paired t-test. h–j Selected metabolites from (a) with corresponding q values shown. Plots were generated using Autoplotter. Average and SEM are plotted. k Joint pathway analysis of transcriptomics and metabolomics data from control and imatinib treated CML CD34+ cells (n = 4 patient-derived samples, 2 µM imatinib for 48 h). Analysis was carried out using MetaboAnalyst 5.0, and hypergeometric test, degree centrality and combined queries were selected. The Benjamini-Hochberg FDR method was used to correct for multiple comparisons. l The TCA cycle from F is shown and significant changes denoted in the key. Source data are provided as a Source Data file.