Fig. 4: MPI KO results in gene expression and metabolic changes consistent with reduced FAO in AML cells. | Nature Communications

Fig. 4: MPI KO results in gene expression and metabolic changes consistent with reduced FAO in AML cells.

From: Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death

Fig. 4: MPI KO results in gene expression and metabolic changes consistent with reduced FAO in AML cells.The alternative text for this image may have been generated using AI.

a GSEA for Oxidative phosphorylation and Fatty acid oxidation signatures from RNA sequencing data comparing MOLM13 NTgRNA and MPIgRNA5 treated with AC220 (left) and MOLM13 MPIgRNA5 treated with AC220 or AC220 and mannose (right), FDR and NES from 1000 permutations; (b) Percentage of TCA cycle intermediates and associated metabolites labelled with ¹³C from ¹³C16-palmitate in MPI KO and NT MOLM13 cells treated with AC220 and mannose as indicated for 24 h along with 50 µM ¹³C16-palmitate. N = 5, 1-way anova with Tukey’s correction; (c) SEAHORSE MitoStress tests showing oxygen consumption rate (OCR) of NTgRNA and MPIgRNA5 MOLM13 cells treated with vehicle, AC220 or AC220 and mannose as indicated after 72 h of treatment, N = 3, 2-way Anova with Sidak’s correction (two left panels). Baseline OCR and ATP production of NTgRNA and MPIgRNA5 MOLM13 cells treated with vehicle, AC220 or AC220 and mannose as indicated after 72 h of treatment, N = 3, 1-way Anova with Tukey’s correction (2 right panels); (d) SEAHORSE MitoStress tests showing OCR comparing MPIgRNA5 cells cultured overnight in substrate limited RPMI media without FBS and glutamine treated with vehicle, AC220, mannose or palmitate (50 µM) as indicated. N = 3, 2-way Anova with Sidak’s correction (two left panels). Baseline OCR and ATP production of NTgRNA and MPIgRNA5 cells treated with palmitate (50 µM) and vehicle, AC220 or mannose as indicated, N = 3, 1-way Anova with Tukey’s correction (2 right panels); (e) SEAHORSE MitoStress tests showing OCR comparing MPIgRNA5 cells treated with AC220, mannose after 72 h in combinations as indicated with or without etomoxir (50 µM), N = 3, 2-way Anova with Sidak’s correction (left panel). Baseline OCR and ATP production of MPI gRNA5 cells treated with vehicle, AC220, mannose after 72 h in combinations as indicated with or without etomoxir (50 µM). N = 3, 1-way Anova with Tukey’s correction (2 right panels); (f) Percentage of live MPIgRNA5 MOLM13 cells treated with vehicle, etomoxir, AC220, mannose or in combinations 6 days after treatment. N = 4, 1-way Anova with Tukey’s correction. For all panels, ns = not significant, *=p < 0.05, **=p < 0.01, ***=p < 0.005, ****=p < 0.001, data presented as mean values ± SEM unless stated.

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