NOTCH1 and acute lymphoblastic leukemia: Owing to ER-calcium release, unfolded and misfolded proteins, such as mutant Notch1, could accumulate in the ER lumen leading to the activation of the unfolded protein response (UPR), ROS production, and apoptosis.34, 41 The interplay between misfolded proteins in the ER, oxidative stress, activation of UPR, and apoptosis has recently been reported.42 This scenario could explain the observed cell death induced by CJ and why the IP3R receptor inhibitor 2-APB and the antioxidant NAC were so effective in blocking this cell death in T-ALL cells.