Figure 4

VPA modifies the expression of pro- and antiapoptotic CLL proteins. mRNA expression was measured by real-time PCR in 10 patients after 24 h of culture in the presence or absence of VPA. (A) bcl-2 expression of treated cells is shown in relation to untreated control cells. Student’s t test values reveal significant values for all tested VPA concentrations: 0.1 mM (P < 0.05), 1 mM (P < 0.001), and 3 mM (P < 0.001). (B) Gene expression values were normalized to gapdh, and the bcl-2/bax ratio was calculated. (C) bcl-2, bax, and bak levels were analyzed by Western blotting of total cellular extracts of CLL cells from 1 representative patient after culture for 3 days. (D) VPA-dependent apoptosis is accompanied by cleavage of BID. CLL cellular extracts were obtained after a 3-day culture in the presence or absence of VPA (2 representative patients are shown). BID and truncated BID (t-BID) were detected by Western blotting.