Novel kinase inhibitors sensitize CLL cells toward ABT-737-mediated apoptosis via UGCG inhibition. (A-B) Quantitative RT-PCR was performed for analysis of UGCG expression (n = 9). The PI3Kδ inhibitor CAL-101 as well as the BTK inhibitor PCI-32765 caused a significant reduction of UGCG expression during BCR cross-linking (P = .0039 for CAL-101 and P = .0078 for PCI-32765). Data are mean ± SEM of 9 independent experiments. Statistics are calculated by Wilcoxon signed-rank test. (C-D) Annexin V/7-amino-actinomycin D staining with subsequent flow cytometry to determine cell viability (n = 15). BCR engagement induced a significant increase of cell survival (P = .001), whereas both CAL-101 and PCI-32765 revealed a similar amount of viable CLL cells as native untreated samples. Although ABT-737 led to a significant reduction of cell survival during BCR stimulation (P < .0001), the combination of both ABT-737 treatment and concomitant kinase inhibition via CAL-101 or PCI-32765, respectively, caused a significant and presumably synergistic apoptotic effect in IgM-stimulated CLL cells (P < .0001 for CAL-101, P = .0004 for PCI-32765). Data are mean ± SEM of 15 independent experiments. Statistics are calculated by paired t test.