The endoplasmic reticulum stress-regulated XBP1s transcription factor drives a negative feedback loop on FLT3 expression in leukemia cells

• XBP1s activation downregulates FLT3 via a novel negative feedback loop • XBP1s induces miR-22-3p, which directly targets and represses FLT3 mRNA • XBP1s expression enhances the efficacy of FLT3 inhibitors in AML models • In vivo, XBP1s boosts therapeutic response to quizartinib (AC220) • Targeting the IRE1α/XBP1s pathway may improve FLT3-directed therapies in AML