Functional roles of MSI2 levels in overcoming chemotherapy resistance of T-ALL. (A) Dose-response matrix (inhibition) of T-ALL cell lines, Jurkat and Molt4, exhibiting in vitro viability profiling after combination treatment with titrated DNR (left panel)/AraC (right panel) and Ro for 72 hours. Experiments were performed in triplicate. Representative dose-response matrixes are shown. Data are presented as mean values ± SEM. (B) Two dimensional synergy map visualization of 2-drug combinational score distribution in T-ALL cell lines, Jurkat and Molt4, based on in vitro dose-response viability profiling after combination treatment with titrated DNR (left panel)/AraC (right panel) and Ro for 72 hours. The synergy score was calculated in reference to highest single-agent (HSA) model. Experiments were performed in triplicate. Representative synergy maps are shown. (C) Distribution of area under curve by dose-response curves of chemotherapeutic drugs from 18 biologically independent primary T-ALL samples are shown in boxplots comparing samples with higher MSI2 mRNA expression (MSI2high, FPKM ≥20.5, n = 9) and those with lower MSI2 mRNA expressions (MSI2low, FPKM <20.5, n = 9). P values were estimated using Mann-Whitney U test; ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001; ns, no significance. (D) Leukemia burden in each subgroup of vehicle (red), Ro (blue), AraC (green), and Ro + AraC (orange) from 2 T-ALL PDX models were tracked weekly as percentage of human cytometric CD45+CD7+ cells in all mononuclear cells in peripheral blood (PB) after red blood cell lysis. (E) Leukemia-free survival estimated for each subgroup of vehicle (red), Ro (blue), AraC (green), and Ro + AraC (orange) from T-ALL PDX models. P values were estimated using Cox regression model. Each treatment group included 6 mice. ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001. (F) Leukemia burden in each subgroup of vehicle (red), Ro (blue), DNR (yellow), and Ro + AraC (purple) from 2 T-ALL PDX models were tracked weekly as percentage of human cytometric CD45+CD7+ cells in all mononuclear cells in the PB after red blood cell lysis. (G) Leukemia-free survival estimated for each subgroup of vehicle (red), Ro (blue), DNR (yellow), and Ro + AraC (purple) from T-ALL PDX models. P values were estimated using Cox regression model. Each treatment group included 6 mice; ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001.

Functional roles of MSI2 levels in overcoming chemotherapy resistance of T-ALL. (A) Dose-response matrix (inhibition) of T-ALL cell lines, Jurkat and Molt4, exhibiting in vitro viability profiling after combination treatment with titrated DNR (left panel)/AraC (right panel) and Ro for 72 hours. Experiments were performed in triplicate. Representative dose-response matrixes are shown. Data are presented as mean values ± SEM. (B) Two dimensional synergy map visualization of 2-drug combinational score distribution in T-ALL cell lines, Jurkat and Molt4, based on in vitro dose-response viability profiling after combination treatment with titrated DNR (left panel)/AraC (right panel) and Ro for 72 hours. The synergy score was calculated in reference to highest single-agent (HSA) model. Experiments were performed in triplicate. Representative synergy maps are shown. (C) Distribution of area under curve by dose-response curves of chemotherapeutic drugs from 18 biologically independent primary T-ALL samples are shown in boxplots comparing samples with higher MSI2 mRNA expression (MSI2high, FPKM ≥20.5, n = 9) and those with lower MSI2 mRNA expressions (MSI2low, FPKM <20.5, n = 9). P values were estimated using Mann-Whitney U test; ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001; ns, no significance. (D) Leukemia burden in each subgroup of vehicle (red), Ro (blue), AraC (green), and Ro + AraC (orange) from 2 T-ALL PDX models were tracked weekly as percentage of human cytometric CD45+CD7+ cells in all mononuclear cells in peripheral blood (PB) after red blood cell lysis. (E) Leukemia-free survival estimated for each subgroup of vehicle (red), Ro (blue), AraC (green), and Ro + AraC (orange) from T-ALL PDX models. P values were estimated using Cox regression model. Each treatment group included 6 mice. ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001. (F) Leukemia burden in each subgroup of vehicle (red), Ro (blue), DNR (yellow), and Ro + AraC (purple) from 2 T-ALL PDX models were tracked weekly as percentage of human cytometric CD45+CD7+ cells in all mononuclear cells in the PB after red blood cell lysis. (G) Leukemia-free survival estimated for each subgroup of vehicle (red), Ro (blue), DNR (yellow), and Ro + AraC (purple) from T-ALL PDX models. P values were estimated using Cox regression model. Each treatment group included 6 mice; ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001.

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