We hypothesize that CD38+ lymphocytes will be more sensitive to the APO866 therapy due to increased intracellular NAD+ consumption as substrate for the PARP dependent DNA repair (instable genome, proliferation). However, CD38+ and CD38- B-CLL cells seem to be equally sensitive to APO866 in vitro. In addition, decreased intracellular NAD+ levels will reduce the anabolism of cADPR. CD38+ can catalyze the synthesis of cADPR from NAD+ and can further hydrolyze cADPR to ADP-ribose.85,86,87 The cADPR is a potent Ca++-mobilizing activator and a potential endogenous regulator.88 The ability of cADPR to release Ca++ from intracellular pools is thought to be part of CD38-mediated signalling pathways that result in cell growth, apoptosis, and differentiation.