Fig. 3: Imatinib disrupts nutrient contribution to TCA cycle in CML CD34+ cells.

a Schematic overview of experimental design. Created with BioRender.com (Agreement number: RE25IF9ZLB). b–d Volcano plots of metabolite fraction labelling from ¹³C₆ glucose (b), ¹³C₅ glutamine (c) and ¹³C₁₆ palmitate (d) comparing control and imatinib treated CML CD34+ cells (n = 4 patients-derived cells per group, 2 µM imatinib for 48 h). Red coloured metabolites have a q value < 0.05 and blue coloured metabolites have a q value < 0.1. Multiple paired t-tests were used and the two-stage step-up (Benjamini, Krieger, and Yekutieli) was used to correct for multiple comparisons. e Fold changes (imatinib/control) for fraction labelling from ¹³C₆ glucose and ¹³C₅ glutamine in CML CD34+ cells (n = 4 patients-derived cells per group, 2 µM imatinib for 48 h). In red are the two metabolites with larger decreases in ¹³C₅ glutamine contribution. Statistical analysis was performed using a single paired t-test (two-sided). f For relative PC/PDH activity CML LSCs (CD34+, n = 4 patients-derived cells per group, 2 µM imatinib for 48 h), the m + 3/m + 2 ratio is shown for the indicated metabolites. Multiple paired t-tests (two-sided) were used and the two-stage step-up (Benjamini, Krieger, and Yekutieli) was used to correct for multiple comparisons. g Fractional labelling from ¹³C₆ glucose for indicated cell fractions (n = 3 patients-derived cells for each group, 2 µM imatinib for 24 h). Average and SEM are plotted, and a two-way ANOVA was used for statistical analysis, p-values were not corrected for multiple comparisons. h Relative PC activity calculated in aspartate in CML LSCs, 2 µM imatinib for 24 h. Statistical analysis was performed using a single paired t-test (two-sided). Source data are provided as a Source Data file.