DDIT3 and acute lymphoblastic leukemia: To further probe the mechanism of MEK/ERK activation in pevonedistat-treated ALL cells, we used lentiviral-based shRNAs to knockdown CHOP expression and block UPR-induced Ca2+ mobilization, and found that down-regulation of CHOP significantly attenuated the induction of p-ERK1/2 by pevonedistat (Figure 2C).