Fig. 3: Response to combination treatment with dexamethasone and tyrosine kinase inhibitors in cell lines.
From: Dasatinib overcomes glucocorticoid resistance in B-cell acute lymphoblastic leukemia
A Expression of signaling molecules in live (cPARP-/cCASP3-) REH GCR cells treated with either vehicle or dexamethasone. Histograms are colored based on mean expression compared to vehicle. B Phosphoproteins expression in live (cPARP−/cCASP3−) REH GCR cells following treatments for 48 h. The red box indicated the most significant treatment as calculated in Supplementary 2C. C tSNE density plots of live REH GCR cells following treatments. In red is highlighted the population emerging after dexamethasone treatment and the numbers indicate the number of cells in the gates D Expression of signaling proteins in NALM6 and REH GCR live cells following treatments for 48 h. Pre-BCR signaling stimulation has been performed treating cells with IgM for 10 min and H2O2 for 5 min. The ratio of the mean expression (arcsin transformed) compared to vehicle is plotted. E Percentage of NALM6 and REH GCR live cells (Ann V-/7AAD- cells) following treatment with five different concentrations of dexamethasone (dex), dasatinib (das), and combinations (n = 36). Red boxes highlight areas of most synergy among drug combinations. F Bliss synergy score (δ score) among dexamethasone and dasatinib combinations in NALM6 (left) and REH GCR (right). G Viability (Ann V-/7AAD- cells) after dexamethasone (dex), dasatinib (das), dexamethasone + dasatinib (dex + das) conditions in NALM6 (left), and REH GCR cells (right). A total of n = 4 independent experiments are plotted as mean ± SEM. Asterisks indicate significant differences between single-drug treatments compared to the combined treatment obtained from ANOVA analysis followed by Tukey’s test (α = 0.05). NALM6: all the comparisons p < 0.0001; REH GCR: all the comparisons p < 0.0001. Veh vehicle, dex dexamethasone, das dasatinib, Ibrut Ibrutinib, Tram Trametinib, Idel Idelalisib, BCR-xL pre-BCR crosslinking. *p ≤ 0.5; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001. Source data are provided as a Source Data file.
