MIF acting as a chaperone of SOD1 mediates MM cell intrinsic resistance to carfilzomib by modulating ROS-induced mitochondrial dysfunction

Abstract

We previously discovered that high levels of macrophage migration inhibitory factor (MIF) were detected in multiple myeloma (MM) and associated with poor survival of patients. Knocking down MIF impaired MM cell adhesion to bone marrow stromal cells in vitro and led to the formation of extramedullary tumors more susceptible to chemotherapeutic treatment. Whether MIF directly regulates MM cell intrinsic resistance to chemotherapy has yet to be explored. We recently identified that MIF-knockout (KO) MM cell lines displayed greater apoptosis than control (CTR)-KO MM cells when treated with proteasome inhibitors, especially carfilzomib (CFZ).