ArticleLeukemia2014
Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 100 citations in OpenAlex.
- More 26S and 30S proteasomes are beneficial in proteinopathy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Bromodomain proteins as potential therapeutic targets for B-cell non-Hodgkin lymphoma.Cell & bioscience · 2024Review
- BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.Genes & diseases · 2023Review
- Long non coding RNAs reveal important pathways in childhood asthma: a future perspective.Journal of molecular histology · 2023Review
- Targeting bromodomain-containing proteins: research advances of drug discovery.Molecular biomedicine · 2023Review
- Catchet-MS identifies IKZF1-targeting thalidomide analogues as novel HIV-1 latency reversal agents.Nucleic acids research · 2022Article
- Functional stratification of cancer drugs through integrated network similarity.NPJ systems biology and applications · 2022Article
- Article
- CDK9 inhibitors in multiple myeloma: a review of progress and perspectives.Medical oncology (Northwood, London, England) · 2022Review
- Epigenetic Small-Molecule Modulators Targeting Metabolic Pathways in Cancer.Sub-cellular biochemistry · 2022Article
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
- miR-22 Modulates Lenalidomide Activity by Counteracting MYC Addiction in Multiple Myeloma.Cancers · 2021Article
- Immunomodulatory Drugs for the Treatment of B Cell Malignancies.International journal of molecular sciences · 2021Review
- Article
- BRD4-mediated repression of p53 is a target for combination therapy in AML.Nature communications · 2021Article
- Management of Drug Resistance in Mantle Cell Lymphoma.Cancers · 2020Review
- Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens.Haematologica · 2020Article
- Impact of HDAC Inhibitors on Protein Quality Control Systems: Consequences for Precision Medicine in Malignant Disease.Frontiers in cell and developmental biology · 2020Review
- Review
- Bromodomain biology and drug discovery.Nature structural & molecular biology · 2019Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bortezomib therapy has shown promising clinical activity in mantle cell lymphoma (MCL), but the development of resistance to proteasome inhibition may limit its efficacy. To unravel the factors involved in the acquisition of bortezomib resistance in vivo, immunodeficient mice were engrafted with a set of MCL cell lines with different levels of sensitivity to the drug, followed by gene expression profiling of the tumors and functional validation of the identified gene signatures. We observed an increased tumorigenicity of bortezomib-resistant MCL cells in vivo, which was associated with plasmacytic differentiation features, like interferon regulatory factor 4 (IRF4) and Blimp-1 upregulation. Lenalidomide was particularly active in this subgroup of tumors, targeting IRF4 expression and plasmacytic differentiation program, thus overcoming bortezomib resistance. Moreover, repression of the IRF4 target gene MYC in bortezomib-resistant cells by gene knockdown or treatment with CPI203, a BET (bromodomain and extra terminal) bromodomain inhibitor, synergistically induced cell death when combined with lenalidomide. In mice, addition of CPI203 to lenalidomide therapy further decreased tumor burden, involving simultaneous MYC and IRF4 downregulation and apoptosis induction. Together, these results suggest that exacerbated IRF4/MYC signaling is associated to bortezomib resistance in MCL in vivo and warrant clinical evaluation of lenalidomide plus BET inhibitor combination in MCL cases refractory to proteasome inhibition.
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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.