Blood: MIF is a biomarker and target for overcoming resistance of multiple myeloma to protease inhibitors

Despite significant progress in biology and chemotherapy, multiple myeloma (MM) is largely incurableThe main problem in theof MMmanagement is the generation of drug resistancethe expression of macrophage migration inhibitors (MIF) in purified MM cells from the source ofrelapsed patients was significantly higher than in patients with persistent remission, and the non-progression survival (PFS) and overall survival (OS) in MM patients with high expression of MIF were significantly shorterMM cell lines also express high levels of MIF, and knocking out MIF makes MM cell lines sensitive to protease inhibitors (PI)-induced apoptosis withnogoing effects on other chemotherapy treatmentsmechanism studies show that MIF can maintain mitochondrial function by inhibiting the production of peroxides during PI processing, thereby protecting MM cells from PI-induced apoptosisSpecifically, MIF, which is present in the form of a pure tripolymer, acts as a molecular companion of superoxide dismutase 1 (SOD1), inhibits PI-induced SOD1 misfolding and maintains SOD1 activityMIF inhibitor 4-IPP and pure tripolymer vinstitutionant ebselen do not kill MM cells, but enhance PI-induced SOD1 misfolding and loss of function, which in turn significantly increases MM cell line and primary MM cell deathmore importantly, inhibiting MIF activity in the body shows collaborative anti-tumor activity with PI, and makes PI-resistant MM cells resensitive to PI therapyGene spectrum data showa a significant negative correlation between the expression of MIF/SOD1 and the responsiveness of MM patients to PI therapyin general, this study reveals the important role of MIF in the sensitivity of MM cells to PI, suggesting that targeting MIF may be a promising treatment strategy that makes MM sensitive to PI therapy