Fig. 7: MPI depletion in primary FLT3ITD AML samples causes ATF6 activation, lipid peroxidation and sensitization to FLT3-TKI therapy. | Nature Communications

Fig. 7: MPI depletion in primary FLT3ITD AML samples causes ATF6 activation, lipid peroxidation and sensitization to FLT3-TKI therapy.

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

Fig. 7: MPI depletion in primary FLT3ITD AML samples causes ATF6 activation, lipid peroxidation and sensitization to FLT3-TKI therapy.The alternative text for this image may have been generated using AI.

a Percentage of live cells of NT shRNA and MPI shRNA1 primary FLT3ITD AML MNC treated with vehicle, AC220 (2.5 nM) or AC220 (2.5 nM) and mannose (100 µM), as indicated normalised to NT shRNA with vehicle for each sample. Treated for 3 days, N = 11, 1 way Anova with Tukey’s correction for multiple comparisons; (b) Percentage of live cells of NT shRNA and MPI shRNA1 normal CD34 + primary cells treated with vehicle, AC220 (2.5 nM) or AC220 (2.5 nM) and mannose (100 µM), as indicated normalised to NT shRNA with vehicle for each sample. Treated for 3 days, N = 3; (c) Mean fluorescence intensity at 510 nm of Bodipy 581/591 C11, which shows level of lipid peroxidation, in NT shRNA and MPI shRNA1 FLT3ITD primary AML MNC treated with vehicle, AC220 (2.5 nM) or AC220 (2.5 nM) and mannose (100 µM), as indicated normalised to NT shRNA with vehicle at 72 h after treatment. N = 4, 1 way Anova with Tukey’s correction for multiple comparisons (left). Representative plots of flow cytometry fluorescence intensity plot NT shRNA and MPI shRNA1 with AC220 (2.5 nM) and mannose (100 µM) as indicated at 510 nm (right); (d) Confocal microscopy images of FLT3ITD primary AML MNC stained for DAPI (blue, 1st column) and ATF6 (green, 2nd column) with a merged image (3rd column), treated with vehicle, AC220 (2.5 nM) and mannose (100 µM) combinations as indicated 72 h after treatment with colocalisation analysis (right graph). N = 6 for all except MPIshRNA with AC220 where N = 7. 1 way Anova with Tukey’s correction; (e) Percentage of live cells of NT shRNA and MPI shRNA1 primary FLT3ITD AML MNC treated with vehicle, AC220 (2.5 nM), Ferrostatin-1 (5 µM) or liproxstatin (1 µM) as indicated, normalised to NT shRNA with vehicle for each sample. Treated for 3 days, N = 3, 1 way Anova with Tukey’s correction for multiple comparisons. For all panels, ns = not significant, *=p < 0.05, **=p < 0.01, ***=p < 0.005, ****=p < 0.001. Source data are provided as a Source Data file. All data presented as mean values ± SEM.

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