However, the BTK inhibitor PCI-32765 induces modest apoptosis in primary CLL cells, which is greater than that observed in normal B cells.24 PCI-32765 also effectively abrogates survival signals provided to CLL cells through various microenvironmental stimuli, including BCR and integrin engagement, soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), and stromal cell contact.24 In addition, PCI-32765 inhibits proliferation of CLL cells induced by CpG oligonucleotides,24 presumably by blocking Toll-like receptor signals that are also transduced through BTK.93 This evidence concerns the gene CD40LG and B-cell chronic lymphocytic leukemia.