ArticleBlood2020
MIF as a biomarker and therapeutic target for overcoming resistance to proteasome inhibitors in human myeloma.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The ubiquitin-proteasome system is an important driver of EBV-associated nasopharyngeal carcinoma progression: a meta-analysis of transcriptomic data.Scientific reports · 2026Pooled it
- MIF-CD74 signaling drives immune modulation in medulloblastoma.Neuro-oncology · 2026Article
- The MIF-CD74 axis drives colorectal cancer via glycolytic reprogramming and is targeted by a novel small-molecule inhibitor.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- comBO: A combined human bone and lympho-myeloid bone marrow organoid for preclinical modeling of hematopoietic disorders.Cell stem cell · 2026Article
- Integrated single-cell and transcriptomic analysis of CD8Translational cancer research · 2026Article
- Single-cell profiling uncovers extracellular vesicle-associated malignant plasma cell subpopulations driving multiple myeloma progression.Frontiers in immunology · 2026Article
- Immunophenotypic changes in the tumor and tumor microenvironment during progression to multiple myeloma.PLoS genetics · 2025Article
- Article
- MitoTracer facilitates the identification of informative mitochondrial mutations for precise lineage reconstruction.PLoS computational biology · 2025Article
- Exploring secondary extramedullary myeloma disease: a five-predictor scoring system with spotlight on double-hit cytogenetics.BMC medicine · 2025Article
- Targeting MTHFD2 alters metabolic homeostasis and synergizes with bortezomib to inhibit multiple myeloma.Cell death discovery · 2025Article
- The CD74 inhibitor DRhQ improves short-term memory and mitochondrial function in 5xFAD mouse model of Aβ accumulation.Metabolic brain disease · 2025Article
- Integrative analysis of Ewing's sarcoma reveals that the MIF-CD74 axis is a target for immunotherapy.Cell communication and signaling : CCS · 2025Article
- STC2+ Malignant Cell State Associated with EMT, Tumor Microenvironment Remodeling, and Poor Prognosis Revealed by Single-Cell and Spatial Transcriptomics in Colorectal Cancer.Oncology research · 2025Article
- Macrophage migration inhibitory factor (MIF) and the tumor ecosystem: a tale of inflammation, immune escape, and tumor growth.Frontiers in immunology · 2025Review
- Identification of Therapy-Induced Clonal Evolution and Resistance Pathways in Minimal Residual Clones in Multiple Myeloma through Single-Cell Sequencing.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Leukocyte immunoglobulin-like receptor B1 (LILRB1) protects human multiple myeloma cells from ferroptosis by maintaining cholesterol homeostasis.Nature communications · 2024Article
- Review
- Monocytes and macrophages: Origin, homing, differentiation, and functionality during inflammation.Heliyon · 2024Review
- CRIP1 involves the pathogenesis of multiple myeloma via dual-regulation of proteasome and autophagy.EBioMedicine · 2024Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Multiple myeloma (MM) remains largely incurable despite significant advances in biotherapy and chemotherapy. The development of drug resistance is a major problem in MM management. Macrophage migration inhibitory factor (MIF) expression was significantly higher in purified MM cells from relapsed patients than those with sustained response, and MM patients with high MIF had significantly shorter progression-free survival (PFS) and overall survival (OS). MM cell lines also express high levels of MIF, and knocking out MIF made them more sensitive to proteasome inhibitor (PI)-induced apoptosis not observed with other chemotherapy drugs. Mechanistic studies showed that MIF protects MM cells from PI-induced apoptosis by maintaining mitochondrial function via suppression of superoxide production in response to PIs. Specifically, MIF, in the form of a homotrimer, acts as a chaperone for superoxide dismutase 1 (SOD1) to suppress PI-induced SOD1 misfolding and to maintain SOD1 activity. MIF inhibitor 4-iodo-6-phenylpyrimidine and homotrimer disrupter ebselen, which do not kill MM cells, enhanced PI-induced SOD1 misfolding and loss of function, resulting in significantly more cell death in both cell lines and primary MM cells. More importantly, inhibiting MIF activity in vivo displayed synergistic antitumor activity with PIs and resensitized PI-resistant MM cells to treatment. In support of these findings, gene-profiling data showed a significantly negative correlation between MIF and SOD1 expression and response to PI treatment in patients with MM. This study shows that MIF plays a crucial role in MM sensitivity to PIs and suggests that targeting MIF may be a promising strategy to (re)sensitize MM to the treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.