New-targeted therapy for leukemia based on Endoplasmic Reticulum Stress

The unfolded protein response (UPR) is an evolutionarily conserved adaptive pathway activated by the stress of the endoplasmic reticulum (ER). ER stress often occurs due to the high protein synthesis in cells and errors made in folding in several diseases such as different cancers and autoimmune diseases. UPR is mediated by three primary arms called inositol-requiring enzyme-1α (IRE1α), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6α (ATF6α). Given that homeostasis in protein synthesis is frequently deregulated in cancers, UPR has a critical role in controlling survival and cell death. Indeed, cancer cells’ resistance to apoptosis is mediated by the pro-survival mechanism of ER stress. Due to the deregulation of UPR signaling in hematopoietic stem cells and leukemia, protein translation will not be set well, and in this time, targeting UPR-driven pro-survival pathways could represent a novel therapeutic strategy in leukemia. This study aims to provide an updated role of UPR as a novel target in leukemia.