Although targeting PERK in vitro by GSK260414 was effective, in vivo application of this PERK inhibitor in ICN1 mice resulted in lethality likely due to a combination of off-target toxicity (e.g. RIPK1 and c-Kit) and organ toxicity (e.g., pancreatic toxicity) that is enhanced in the setting of leukemia 55-57. Here, RIPK1 is linked to leukemia.