Expression of cereblon protein assessed by immunohistochemicalstaining in myeloma cells is associated with superior response of thalidomide- and lenalidomide-based treatment, but not bortezomib-based treatment, in patients with multiple myeloma
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Cereblon (CRBN) is essential for the anti-myeloma (MM) activity of immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide. However, the clinical implications of CRBN in MM patients are unclear. Using immunohistochemical (IHC) staining on paraffin-embedded bone marrow sections, the expression of CRBN protein in myeloma cells (MCs) was assessed in 40 relapsed/refractory MM (RRMM) patients who received lenalidomide/dexamethasone (LD) and 45 and 22 newly diagnosed MM (NDMM) patients who received thalidomide/dexamethasone (TD) and melphalan/bortezomib/prednisolone (MVP), respectively. IHC staining were scored on a scale representing the diffuseness and intensity of positive-staining MCs (range, 0-8) and a score ≥4.5 was used for CRBN positivity (CRBN(+)) on a cut-point analysis of all possible scores and response of TD and LD. Compared to CRBN(+) NDMM patients, CRBN(-) NDMM patients had more international staging system (ISS) III (26 vs. 61 %, respectively; P = 0.006). In the LD and TD cohorts, the response rate (RR) was higher in CRBN(+) patients than CRBN(-) patients (LD 79 vs. 33 %, respectively; P = 0.005) (TD 75 vs. 29 %, respectively; P = 0.005); however, this trend was not observed in the MVP cohort. In the LD and TD cohorts, the positive and negative prediction value of CRBN(+) for treatment response was 79 and 67 % and 75 and 71 %, respectively. Multivariate analysis showed that CRBN(+) was a significant factor associated with superior RR for LD and TD. The data suggest that expression of CRBN protein in MCs assessed using the IHC is a feasible approach to predict the response of IMiDs in MM patients.
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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 [152]
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- Authors
- Huang, S.-Y., Lin, C.-W., Lin, H.-H., Yao, M., Tang, J.-L., Wu, S.-J., Chen, Y.-C., Lu, H.-Y., Hou, H.-A., Chen, C.-Y., Chou, W.-C., Tsay, W., Chou, S.-J., & Tien, H.-F.
- Affiliations
- National Taiwan University Hospital (TW)
- Corresponding author
- Huang, Shang-Yi
- ORCID
- Venue
- Annals of Hematology
- Published
- 2014-04-01
- Volume
- 93
- Issue
- 8
- Pages
- 1371-1380
- ISSN
- 0939-5555 (ISSN-L)
- 1432-0584
- PMC
- PMC4082140
- OpenAlex
- W2025030626
- Cited by
- 62
- References
- 37
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 11 · 2019: 7 · 2018: 10 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 3
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Annals of Hematology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Council (NSC101-2325-B-002-078)
- National Research Program for Biopharmaceuticals (NSC101-2325-B-002-078)
- National Taiwan University Hospital
- National Taiwan University
- 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 › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- cereblon, multiple myeloma, immunomodulators, thalidomide, lenalidomide, bortezomib, treatment response prediction, newly diagnosed multiple myeloma, relapsed/refractory multiple myeloma, prognostic factors
- MeSH terms
- Bortezomib, Lenalidomide, Aged, Antineoplastic Combined Chemotherapy Protocols, Bone Marrow Examination, Boronic Acids, Dexamethasone, Female, Follow-Up Studies, Humans, Male, Melphalan, Middle Aged, Multiple Myeloma, Neoplasm Proteins, Peptide Hydrolases, Prednisolone, Pyrazines, Thalidomide, Neoplastic Stem Cells, Survival Analysis, Paraffin Embedding, Salvage Therapy, Treatment Outcome, Angiogenesis Inhibitors, Gene Expression Profiling, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Syndecan-1
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