Figure 6. The combination of TAK-659 with fludarabine, ibrutinib or idelalisib synergistically induces apoptosis in proliferative CLL cells.
Primary CLL cells from 12 patients were pre-treated with 0.1 μM TAK-659 and increasing doses of fludarabine (A), ibrutinib (B) or idelalisib (C) for 1 hour and co-cultured for 48 hours. LD50 for every treatment cohort were calculated and compared (*P < 0.05, **P < 0.01, ***P < 0.001, two-way ANOVA, Bonferroni's post -test. Graph shows mean ± SEM). (D) Calculated combination index values are plotted. (E) Primary CLL cells from 6 patients were pre-treated with 1 μM ibrutinib or 1 μM TAK-659 and cultured with CD40L 1 μg/mL. After 4 days, 1 μM TAK-659 was added to ibrutinib-treated cells. Viability of primary CLL cells was analyzed by Annexin V and PI staining by FC at the indicated time points. (*P < 0.05, ***P < 0.001, paired T-test. Wilcoxon post-test).