High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone
Open accessAbstract
Summary: Cereblon (CRBN) has recently been identified as a target for immunomodulatory drugs (IM i D s) and its downregulation has been linked to resistance to lenalidomide. Here, we studied CRBN expression by real time polymerase chain reaction in 49 bone marrow samples of newly diagnosed patients with multiple myeloma treated with lenalidomide and dexamethasone. Median CRBN expression was 3·45 in patients who achieved complete response, and 3·75, 2·01, 0·78, and 0·70 in those with very good partial response, partial response, stable disease and progressive disease respectively. CRBN expression levels correlated significantly with response to lenalidomide treatment (r = 0·48; P < 0·001). Among established prognostic parameters, only beta‐2‐microglobulin correlated with cereblon (r = 0·66; P < 0·001). A close association of CRBN with interferon regulatory factor 4 (IRF 4) (P < 0·001) and with CTNNB 1 (P < 0·001) was found. Overall, a statistically significant association between baseline CRBN expression and response in MM patients treated with lenalidomide is shown. CRBN expression is closely associated with IRF 4, which is an important target of IM i D therapy.
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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 [154]
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- Authors
- Heintel, D., Rocci, A., Ludwig, H., Bolomsky, A., Caltagirone, S., Schreder, M., Pfeifer, S., Gisslinger, H., Zojer, N., Jäger, U., & Palumbo, A.
- Affiliations
- Wilhelminen Hospital (AT)
- Azienda Ospedaliero Universitaria San Giovanni Battista (IT)
- Medical University of Vienna (AT)
- Division of Haematology and Haemostaseology Department of Medicine I Medical University of Vienna (MUW) Vienna Austria
- Corresponding author
- Ludwig, Heinz
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2013-04-09
- Volume
- 161
- Issue
- 5
- Pages
- 695-700
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- OpenAlex
- W2049005444
- Cited by
- 128
- References
- 30
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 10 · 2021: 16 · 2020: 3 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 8 · 2015: 13 · 2014: 10 · 2013: 14 · 2012: 3
- FWCI
- 10.75
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Celgene
- 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, lenalidomide, dexamethasone, immunomodulators, treatment response, prognostic factors, IRF4, beta2-microglobulin, CTNNB1, lenalidomide resistance
- MeSH terms
- Lenalidomide, Interferon Regulatory Factor-4, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Bone Marrow, Dexamethasone, Humans, Middle Aged, Multiple Myeloma, Neoplasm Proteins, Peptide Hydrolases, Plasma Cells, Prognosis, Retrospective Studies, Thalidomide, Tumor Cells, Cultured, Biomarkers, Tumor, Treatment Outcome, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Interferon Regulatory Factors, beta Catenin, Real-Time Polymerase Chain Reaction
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