ArticleOncotarget2016
CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Genetic mutations and features of mantle cell lymphoma: a systematic review and meta-analysis.Blood advances · 2020Pooled it
- Genomic landscape of patients in a phase II study of zanubrutinib in ibrutinib- and/or acalabrutinib-intolerant patients with B-cell malignancies.Haematologica · 2024Trial
- Genomic and transcriptomic profiling reveals distinct molecular subsets associated with outcomes in mantle cell lymphoma.The Journal of clinical investigation · 2022Trial
- Surveying the Genomic Landscape of Mantle Cell Lymphoma Indicates the Importance of Multimodal Genomic and Transcriptomic Exploration.medRxiv : the preprint server for health sciences · 2026Article
- Cyclin-Dependent Kinase 5 Contributes to Bruton's Tyrosine Kinase Inhibitor Resistance via the IRE1α/XBP1 Axis in Mantle Cell Lymphoma.Research square · 2026Article
- Functional genomics and tumor microenvironment analysis reveal prognostic biological subtypes in Mantle cell lymphoma.Nature communications · 2025Article
- PAX Family, Master Regulator in Cancer.Diagnostics (Basel, Switzerland) · 2025Review
- CEACAM1 as a mediator of B-cell receptor signaling in mantle cell lymphoma.Nature communications · 2025Article
- "The End of the Golden Weather": therapeutic strategies for mantle cell lymphoma relapsed or refractory to covalent BTK inhibitors.Haematologica · 2025Review
- Assessment of Cyclin D1 Expression: Prognostic Value and Functional Insights in Endometrial Cancer: In Silico Study.International journal of molecular sciences · 2025Article
- Biological and clinical determinants shaping heterogeneity in mantle cell lymphoma.Blood advances · 2024Review
- Navigating Lymphomas through BCR Signaling and Double-Hit Insights: Overview.Hematology reports · 2024Review
- Targeting BTK in B Cell Malignancies: From Mode of Action to Resistance Mechanisms.International journal of molecular sciences · 2024Review
- Empowering macrophages: the cancer fighters within the tumour microenvironment in mantle cell lymphoma.Frontiers in immunology · 2024Review
- Beyond Bruton's tyrosine kinase inhibitors in mantle cell lymphoma: bispecific antibodies, antibody-drug conjugates, CAR T-cells, and novel agents.Journal of hematology & oncology · 2023Review
- The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL.Cancers · 2023Article
- Evaluation and Application of Drug Resistance by Biomarkers in the Clinical Treatment of Liver Cancer.Cells · 2023Review
- Structural Complementarity of Bruton's Tyrosine Kinase and Its Inhibitors for Implication in B-Cell Malignancies and Autoimmune Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Resistance to Bruton tyrosine kinase inhibition in chronic lymphocytic leukaemia and non-Hodgkin lymphoma.British journal of haematology · 2023Review
- Treatment of Mantle Cell Lymphoma in the Frontline Setting: Are We Ready for a Risk-Adapted Approach?Journal of personalized medicine · 2022Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation, which leads to deregulated expression of the cell cycle regulatory protein cyclin D1 (CCND1). Genomic studies of MCL have also identified recurrent mutations in the coding region of CCND1. However, the functional consequence of these mutations is not known. Here, we showed that, compared to wild type (WT), single E36K, Y44D or C47S CCND1 mutations increased CCND1 protein levels in MCL cell lines. Mechanistically, these mutations stabilized CCND1 protein through attenuation of threonine-286 phosphorylation, which is important for proteolysis through the ubiquitin-proteasome pathway. In addition, the mutant proteins preferentially localized to the nucleus. Interestingly, forced expression of WT or mutant CCND1 increased resistance of MCL cell lines to ibrutinib, an FDA-approved Bruton tyrosine kinase inhibitor for MCL treatment. The Y44D mutant sustained the resistance to ibrutinib even at supraphysiologic concentrations (5-10 μM). Furthermore, primary MCL tumors with CCND1 mutations also expressed stable CCND1 protein and were resistant to ibrutinib. These findings uncover a new mechanism that is critical for the regulation of CCND1 protein levels, and is directly relevant to primary ibrutinib resistance in MCL.
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Registered trials
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.