Fig. 6: VXL and IACS-010759 induce profound metabolic damage in vivo and leads to improvement of tumor burden reduction and overall survival in PDX models in vivo. | Nature Communications

Fig. 6: VXL and IACS-010759 induce profound metabolic damage in vivo and leads to improvement of tumor burden reduction and overall survival in PDX models in vivo.

From: Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia

Fig. 6

a MS Heatmap of metabolites in BM of mice transplanted with NOTCH1-mutated PDX80 after 12 h of treatment with vehicle, IACS-010759, VXL, or the combination of IACS-010759 and VXL (n = 2). b CyTOF heatmap of spleen samples from PDX80 model treated with vehicle, IACS-010759, VXL, or the combination of IACS-010759 and VXL (n = 2). c CyTOF UMAP for CD45, CD3, CD5, CD7 and Ki67 markers in spleen samples from PDX80 model treated with vehicle, IACS-010759, VXL, or the combination of IACS-010759 and VXL (n = 2). d Gene expression analysis of spleen samples from PDX80 model after treatment with the combination of IACS-010759 and VXL compared to vehicle treatment. e Leukemic engraftment (% of human CD45+ leukemia cells) in spleen at day 5 of treatment with vehicle, VXL, IACS-010759, or the combination of IACS-010759 and VXL, as measured by FL in 3 PDX models (from left to right: PDX D115, PDX CU76, PDX 80) (mean ± SD, n = 4 individual mice per treatment arm); one-way ANOVA; *p = 0.01; **p = 0.0016; ***p = 0.0002, ****p < 0.0001. f Tumor burden development in 3 PDX models (from left to right: PDX D115, PDX CU76, PDX 80) measured as weekly detection of circulating human CD45+ cells in peripheral blood (PB) and expressed as percent of normalized human to sum of human and murine CD45+ cells in mice undergoing treatment with vehicle, IACS-010759 (5 mg/kg once daily, 5 days on/2 days off), VXL (once weekly), or the combination of IACS-010759 and VXL (mean ± SD, n = 10 mice per treatment arm for PDX D115 and PDX CU76 and n = 8 mice per treatment arm for PDX 80). g Kaplan–Meier survival curves of mice transplanted with PDX models (from left to right: PDX D115, PDX CU76, PDX 80) and treated with vehicle, IACS-010759, VXL, or the combination of IACS-010759 and VXL (n = 8). Treatment was initiated once the level of circulating leukemia cells in PB reached 0.5–1%; the timeframe of treatment is labeled by the yellow windows on the graphs. log-rank test: ***p < 0.0006 ****p < 0.0001.

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