The clinical significance of cereblon expression in multiple myeloma
Open accessAbstract
Cereblon (CRBN) mediates immunomodulatory drug (IMiD) action in multiple myeloma (MM). We demonstrate here that no patient with very low CRBN expression responded to IMiD plus dexamethasone therapy. In 53 refractory MM patients treated with pomalidomide and dexamethasone, CRBN levels predict for decreased response rates and significant differences in PFS (3.0 vs. 8.9 months, p<0.001) and OS (9.1 vs. 27.2 months, p=0.01) (lowest quartile vs. highest three quartiles). While higher CRBN levels can serve as a surrogate for low risk disease, our study demonstrates that low CRBN expression can predict resistance to IMiD monotherapy and is a predictive biomarker for survival outcomes.
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CRBN expression levels in patient samples have been positively associated with sensitivity to thalidomide analogues in some studies but not in others.
“CRBN expression levels in patient samples has been positively associated with sensitivity to thalidomide analogues in some studies149–154, but not in others155,156.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [156]
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- Authors
- Schuster, S. R., Kortuem, K. M., Zhu, Y. X., Braggio, E., Shi, C.-X., Bruins, L. A., Schmidt, J. E., Ahmann, G., Kumar, S., Rajkumar, S. V., Mikhael, J., LaPlant, B., Champion, M. D., Laumann, K., Barlogie, B., Fonseca, R., Bergsagel, P. L., Lacy, M., & Stewart, A. K.
- Affiliations
- University of Colorado Health (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic (US)
- Corresponding author
- Schuster, Steven R.
- ORCID
- Venue
- Leukemia Research
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 38
- Issue
- 1
- Pages
- 23-28
- ISSN
- 0145-2126 (ISSN-L)
- PMC
- PMC3905958
- OpenAlex
- W2059837228
- Cited by
- 113
- References
- 24
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 8 · 2023: 3 · 2022: 10 · 2021: 8 · 2020: 4 · 2019: 12 · 2018: 14 · 2017: 7 · 2016: 12 · 2015: 8 · 2014: 11 · 2013: 2 · 2012: 1
- FWCI
- 7.89
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Leukemia Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Minneapolis Medical Research Foundation
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- cereblon, multiple myeloma, immunomodulators, pomalidomide, dexamethasone, treatment response prediction, predictive biomarkers, progression-free survival, overall survival, drug resistance
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Humans, Multiple Myeloma, Peptide Hydrolases, Prognosis, Thalidomide, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Survival Analysis, Treatment Outcome, Drug Resistance, Neoplasm, Ubiquitin-Protein Ligases, Cell Line, Tumor, Adaptor Proteins, Signal Transducing
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