Figure 7.

Schematic diagram summarizing our working model. Hypothetical association of ER stress/NOTCH1 signaling with susceptibility to ER stress-induced apoptosis in CLL with dysregulated NOTCH1. CLL cells harboring NOTCH1 mutation (NT1-M) show higher basal levels of ER stress than NOTCH1-WT (NT1-WT) cells. ER stress-inducing drugs further increase ER stress in NT1-M CLL cells and induce high levels of apoptosis, which are accompanied by decreased NOTCH1 signaling activation. Conversely, NT1-WT CLL cells respond to ER stressors with a moderate ER stress, low levels of apoptosis, and increased NOTCH1 activation, which probably serves to counteract ER stress.