Biological effects of dasatinib and combination with fludarabine treatment. Freshly isolated CLL cells (A) and the cell lines JVM-3 and Mec1 (B) were treated with the indicated doses of dasatinib or fludarabine or a combination of the indicated fludarabine concentrations and 5 μM dasatinib and analyzed for annexin V-staining after 48 hours. In addition to apoptosis induction, the influence of dasatinib on the metabolic activity of prolymphocytic cell lines was assessed by the XTT assay (C). Dose-dependent dasatinib effects on cellular respiration in PBMCs from healthy donors and a CLL patient were compared (D). Apoptosis induction by 5 μM dasatinib was assessed in 12 CLL patient samples by flow cytometric analysis after annexin V and DiOC6 staining. In 9 CLL cell samples the investigation was extended to treatment with 5 μM fludarabine and the combination of dasatinib and fludarabine (E). Error bars represent SD.
