Mechanism of apoptosis induction by dasatinib in CLL cells. Apoptosis induction by 5 μM dasatinib was confirmed in patient samples and prolymphocytic cell lines by cleavage of the caspase substrate PARP demonstrated by Western blot analysis (A). The amounts of uncleaved (uc) and cleaved (c) caspase forms, and expression levels of the antiapoptotic bcl-2 family members Mcl-1 and Bcl-x_L, and of p53 in the absence (−) or presence (+) of 5 μM dasatinib were recorded in primary CLL cells (B) and the prolymphocytic cell lines JVM-3 and Mec1 (C). In these cell lines, dasatinib effects on the expression levels of proapoptotic bcl-2 family proteins and on cytoplasmic cytochrome c levels were monitored (D).