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Fig. 2 | Journal of Hematology & Oncology

Fig. 2

From: PSEN1-selective gamma-secretase inhibition in combination with kinase or XPO-1 inhibitors effectively targets T cell acute lymphoblastic leukemia

Fig. 2

MRK-560 and tyrosine kinase inhibitors synergistically inhibit proliferation in vitro. a Dose–response curve for ruxolitinib treatment on DND-41, LOUCY and RPMI-8402 after 48-h incubation. Data represent mean of 3 experiments. b Growth curves for DND-41, RPMI-8402 and LOUCY T-ALL cell lines. Growth medium was supplemented with DMSO, MRK-560 100 nM, ruxolitinib 1 µM or both compounds. Data represent mean ± standard deviation for biological triplicates. c Bar chart showing relative cell number of DND-41 cells after 48-h incubation with different ruxolitinib concentrations following 7-day pretreatment with DMSO, MRK-560 0,1 µM or 1 µM. Bars represent mean, standard deviation is noted. Data are representative of biological triplicates. Data were analyzed using one-way ANOVA with Bonferroni multiple comparisons correction. d Annexin V-PI staining in DND41 T-ALL cells after 12 days of treatment with DMSO, ruxolitinib (1 µM), MRK-560 (1 µM) or combination. Data represent mean ± standard deviation for biological triplicates. Data were analyzed using one-way ANOVA with Bonferroni multiple comparisons correction. e Chou–Talalay plot for DND-41 showing the combined effect of MRK-560 and ruxolitinib after 48-h incubation. CompuSyn was used to calculate the combination index (CI). CI < 1, CI = 1 and CI > 1 indicates synergistic, additive and antagonistic effects, respectively. f Dose–response curve for imatinib treatment on ALL-SIL, LOUCY and RPMI-8402 after 48-h incubation. Data represent mean of 3 experiments. g Growth curves for ALL-SIL, RPMI-8402 and LOUCY T-ALL cell lines. Growth medium was supplemented with DMSO, MRK-560 100 nM, imatinib 10 nM or both compounds. Data represent mean ± standard deviation for biological triplicates. h Bar chart showing relative cell number of ALL-SIL cells after 48-h incubation with different concentrations of imatinib following 7-day pretreatment with DMSO, MRK-560 0,1 µM or 1 µM. Bars represent mean, standard deviation is marked. Data represent biological triplicates. Data were analyzed using one-way ANOVA with Bonferroni multiple comparisons correction. i Chou–Talalay plot showing the combined effect of MRK-560 and imatinib after 48-h incubation of ALL-SIL. CompuSyn was used to calculate the combination index (CI). **p < 0.01, ***p < 0.001, ****p < 0.0001

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