ArticleLeukemia2016
Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?Frontiers in oncology · 2021Pooled it
- Trial
- Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.Haematologica · 2026Article
- Article
- Monocyte-mediated metabolic rewiring via CD31-CD38 interactions promotes growth and drug-resistance in multiple myeloma.HemaSphere · 2026Article
- Promoter hypomethylation drives ABCB1-mediated carfilzomib resistance in multiple myeloma.Clinical epigenetics · 2026Article
- Carfilzomib resistance in multiple myeloma: A comparative metabolomic analysis.Journal of applied genetics · 2025Article
- Mitochondrial fission factor drives an actionable metabolic vulnerability in multiple myeloma.Haematologica · 2025Article
- Article
- Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Microbiota-derived urolithin A in monoclonal gammopathies and multiple myeloma therapy.Microbiome · 2025Article
- Metabolic reprogramming induced by PSMA4 overexpression facilitates bortezomib resistance in multiple myeloma.Annals of hematology · 2025Article
- A thematic analysis of prognostic, diagnostic, and therapeutic of circulating miRNA biomarkers in bortezomib-resistant multiple myeloma.SAGE open medicine · 2025Review
- Lipid metabolism in multiple myeloma: pathogenesis, therapeutic opportunities, and future directions.Frontiers in oncology · 2025Review
- Article
- Characterization of driver mutations identifies gene signatures predictive of prognosis and treatment sensitivity in multiple myeloma.The oncologist · 2024Article
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Proteasome and PARP1 dual-target inhibitor for multiple myeloma: Fluzoparib.Biochemistry and biophysics reports · 2024Article
- Progression of monoclonal gammopathy of undetermined significance to multiple myeloma is associated with enhanced translational quality control and overall loss of surface antigens.Journal of translational medicine · 2024Article
33 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptive resistance of myeloma to proteasome inhibition represents a clinical challenge, whose biology is poorly understood. Proteasome mutations were implicated as underlying mechanism, while an alternative hypothesis based on low activation status of the unfolded protein response was recently suggested (IRE1/XBP1-low model). We generated bortezomib- and carfilzomib-adapted, highly resistant multiple myeloma cell clones (AMO-BTZ, AMO-CFZ), which we analyzed in a combined quantitative and functional proteomic approach. We demonstrate that proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition, irrespective of a proteasome mutation, and uniformly show an 'IRE1/XBP1-low' signature. Adaptation of myeloma cells to proteasome inhibitors involved quantitative changes in >600 protein species with similar patterns in AMO-BTZ and AMO-CFZ cells: proteins involved in metabolic regulation, redox homeostasis, and protein folding and destruction were upregulated, while apoptosis and transcription/translation were downregulated. The quantitatively most upregulated protein in AMO-CFZ cells was the multidrug resistance protein (MDR1) protein ABCB1, and carfilzomib resistance could be overcome by MDR1 inhibition. We propose a model where proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition owing to metabolic adaptations that favor the generation of reducing equivalents, such as NADPH, which is supported by oxidative glycolysis. Proteasome inhibitor resistance may thus be targeted by manipulating the energy and redox metabolism.
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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.