Earlier studies focused on how the AMP-activated kinase (AMPK) activator 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR [144]) in combination with either methotrexate or 2-deoxy-D-glucose (2-DG, a sugar analog that inhibits both glycolysis and N-linked glycosylation [145]), induced a prolonged ER stress in B-ALL cells, thereby leading to proapoptotic UPR via IRE1α, GRP78, phosphorylated eIF2α, and CHOP [146]. Here, HSPA5 is linked to precursor B-cell acute lymphoblastic leukemia.