Absence of mutations in cereblon (CRBN) and DNA damage-binding protein 1 (DDB1) genes and significance for IMiD therapy
Open accessAbstract
Thalidomide and the IMiD immunomodulatory drugs, lenalidomide and pomalidomide, are widely used in the treatment of multiple myeloma (MM), del(5q) myelodysplastic syndromes and other hematologic malignancies, including mantle cell lymphoma. Ito et al. 1 recently identified cereblon as a key target of thalidomide. Subsequent studies confirmed cereblon to be a common target for lenalidomide and pomalidomide, and established its essential role in mediating anticancer and immunomodulatory effects of these drugs. 2 , 3 Cereblon is encoded by the CRBN gene on chromosome 3 containing 11 exons, and the fully spliced transcript produces a 51-kDa protein. Cereblon is a component of the cullin ring E3 ubiquitin ligase complex (CRL4 CRBN ) that also contains DNA damage-binding protein 1 (DDB1), cullin (Cul) 4a and regulator of cullins (Roc) 1. 1 E3 ligases attach ubiquitin moieties to specific substrate proteins in the cell that can mark them for proteasomal degradation. The putative role of cereblon within the E3 ligase complex is that of a substrate receptor.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [150]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 13 · Cited by 56
- Authors
- Thakurta, A., Gandhi, A. K., Waldman, M. F., Bjorklund, C., Ning, Y., Mendy, D., Schafer, P., Lopez-Girona, A., Lentzsch, S., Schey, S. A., Calle, Y., Chelliah, R., Orlowski, R. Z., Madan, A., Avet-Loiseau, H., & Chopra, R.
- Affiliations
- Celgene (United States) (US)
- Columbia University (US)
- King's College London (GB)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Chopra, R
- ORCID
- Venue
- Leukemia
- Published
- 2013-10-29
- Volume
- 28
- Issue
- 5
- Pages
- 1129-1131
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- PMC
- PMC4017253
- OpenAlex
- W2081045803
- Cited by
- 56
- References
- 13
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 1
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Leukemia (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Celgene
- Cancer Research UK (11566)
- Imperial College London
- National Cancer Institute (P50CA142509, P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- cereblon, DDB1, lenalidomide, pomalidomide, thalidomide, immunomodulators, multiple myeloma, del(5q) myelodysplastic syndrome, mantle cell lymphoma, ubiquitination, substrate receptor, germline mutations
- MeSH terms
- Lenalidomide, Adjuvants, Immunologic, DNA-Binding Proteins, Humans, Mutation, Peptide Hydrolases, Thalidomide, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
