ArticleLeukemia2011
Activation of the p53 pathway by the MDM2 inhibitor nutlin-3a overcomes BCL2 overexpression in a preclinical model of diffuse large B-cell lymphoma associated with t(14;18)(q32;q21).
Article in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- Lnc00892 enhances cisplatin sensitivity by inducing apoptosis through the BTAF1/MDM2/STAT5B/XIAP axis in bladder cancer cells.Biology direct · 2026Article
- GD3 synthase drives resistance to p53-induced apoptosis in breast cancer by modulating mitochondrial function.Oncogene · 2025Article
- Detection ofInternational journal of molecular sciences · 2025Article
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- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Pharmacological Inhibition of MDM2 Induces Apoptosis in p53-Mutated Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- Multiomics Analysis of Exportin Family Reveals XPO1 as a Novel Target for Clear Cell Renal Cell Carcinoma.International journal of genomics · 2025Article
- Comparative Copy Number Variation Profiling of GL01, an Immortalized Non-small Cell Lung Cancer Cell Line Derived from a Filipino Patient, and A549 Lung Adenocarcinoma Cells.Acta medica Philippina · 2025Article
- Targeting MDM2 in malignancies is a promising strategy for overcoming resistance to anticancer immunotherapy.Journal of biomedical science · 2024Review
- Machine Learning Algorithms Identify Target Genes and the Molecular Mechanism of Matrine against Diffuse Large B-cell Lymphoma.Current computer-aided drug design · 2024Article
- Progress in deciphering the role of p53 in diffuse large B-cell lymphoma: mechanisms and therapeutic targets.American journal of cancer research · 2024Review
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- Genome-wide CRISPR screening reveals ADCK3 as a key regulator in sensitizing endometrial carcinoma cells to MPA therapy.British journal of cancer · 2023Article
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- Decreased RNA‑binding protein IGF2BP2 downregulates NT5DC2, which suppresses cell proliferation, and induces cell cycle arrest and apoptosis in diffuse large B‑cell lymphoma cells by regulating the p53 signaling pathway.Molecular medicine reports · 2022Article
- IDO1 plays a tumor-promoting role via MDM2-mediated suppression of the p53 pathway in diffuse large B-cell lymphoma.Cell death & disease · 2022Article
- Epstein Barr virus-positive B-cell lymphoma is highly vulnerable to MDM2 inhibitors in vivo.Blood advances · 2022Article
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- The Ubiquitin System: An Emerging Therapeutic Target for Lung Cancer.International journal of molecular sciences · 2021Review
- Review
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
p53 is frequently wild type (wt) in diffuse large B-cell lymphoma (DLBCL) associated with t(14;18)(q32;q21) that overexpresses BCL2. Nutlin-3a is a small molecule that activates the p53 pathway by disrupting p53-MDM2 interaction. We show that nutlin-3a activates p53 in DLBCL cells associated with t(14;18)(q32;q21), BCL2 overexpression and wt p53, resulting in cell cycle arrest and apoptosis. Nutlin-3a treatment had similar effects on DLBCL cells of activated B-cell phenotype with wt p53. Cell cycle arrest was associated with upregulation of p21. Nutlin-3a-induced apoptosis was accompanied by BAX and PUMA upregulation, BCL-XL downregulation, serine-70 dephosphorylation of BCL2, direct binding of BCL2 by p53, caspase-9 upregulation and caspase-3 cleavage. Cell death was reduced when p53-dependent transactivation activity was inhibited by pifithrin-α (PFT-α), or PFT-μ inhibited direct p53 targeting of mitochondria. Nutlin-3a sensitized activation of the intrinsic apoptotic pathway by BCL2 inhibitors in t(14;18)-positive DLBCL cells with wt p53, and enhanced doxorubicin cytotoxicity against t(14;18)-positive DLBCL cells with wt or mutant p53, the latter in part via p73 upregulation. Nutlin-3a treatment in a xenograft animal lymphoma model inhibited growth of t(14;18)-positive DLBCL tumors, associated with increased apoptosis and decreased proliferation. These data suggest that disruption of the p53-MDM2 interaction by nutlin-3a offers a novel therapeutic approach for DLBCL associated with t(14;18)(q32;q21).
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