Model for GA101-induced cell death in CD40-stimulated CLL cells. GA101 induces HA, which can be blocked by cytoD. CD40 stimulation increases the number of lysosomes that are susceptible to swelling and burst via GA101 engagement. Both GA101-induced HA and an increase in lysosomal number are required to result in LMP, leading to cell death. An increase in lysosomal volume and LMP can be inhibited by concA. Release of cathepsins into the cytosol after LMP leads to caspase activation. Caspase activation, but not cell death, is inhibited by Z-VAD and Q-VD.