Type I but Not Type II Calreticulin Mutations Activate the IRE1α/XBP1 Pathway of the Unfolded Protein Response to Drive Myeloproliferative Neoplasms.
Juan IbarraYassmin A ElbannaKatarzyna KurylowiczMichele CiboddoHarrison S GreenbaumNicole S ArellanoDeborah RodriguezMaria EversAlthea Bock-HughesChenyu LiuQuinn SmithJulian LutzeJulian BaumeisterMilena KalmerKathrin OlschokBenjamin NicholsonDiane SilvaLuke MaxwellJonathan DowgielewiczElisa RumiDaniela PietraIlaria Carola CasettiSilvia CatricalaSteffen KoschmiederSandeep K GurbuxaniRebekka K SchneiderScott A OakesShannon E ElfPublished in: Blood cancer discovery (2022)
Current targeted therapies for CALR-mutated MPNs are not curative and fail to differentiate between type I- versus type II-driven disease. To improve treatment strategies, it is critical to identify CALR mutation type-specific vulnerabilities. Here we show that IRE1α/XBP1 represents a unique, targetable dependency specific to type I CALR-mutated MPNs. This article is highlighted in the In This Issue feature, p. 265.