Figure 7

The combination of HDAC inhibitors and autophagy inhibitors synergistically/additively kills CLL cells at clinically relevant concentrations. Combination analyses were performed following the median-effect method.¹⁹ PBMCs from CLL patients (n=5) were exposed to an HDAC inhibitor (MGCD0103 (MGCD) or VPA) and an autophagy inhibitor (chloroquine (CQ) or 3-MA) simultaneously for 48 h. Various concentrations of HDAC inhibitors (shown as blue dots or red squares, and increasing from left to right along the x axis) were combined with fixed doses of CQ (5 and 10 μmol/l) or 3-MA (0.3 and 0.6 mmol/l). (a, b) The concentrations of MGCD0103 used for these experiments were (in μmol/l) 0.05, 0.1, 0.2, 0.4, 0.8 and 1.6, and (c, d) those of VPA were (in mmol/l) 0.25, 0.5, 1, 2, 4 and 8. CIs for different levels of cell death (fraction affected) were calculated using the CompuSyn software. CI<1, CI=1 and CI>1 indicate synergism, additive effect and antagonism, respectively.