ArticleOncotarget2017
Epstein-Barr virus EBNA2 directs doxorubicin resistance of B cell lymphoma through CCL3 and CCL4-mediated activation of NF-κB and Btk.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Mechanisms of first-line treatment resistance in diffuse large B-cell lymphoma.Frontiers in immunology · 2026Review
- Exhausted CD4Frontiers in immunology · 2026Article
- Epstein-Barr virus: biology, pathogenesis and therapy of lymphomas.Discover oncology · 2025Review
- Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches.Cells · 2025Review
- Epstein-Barr virus-encoded EBNA2 downregulates ICOSL by inducing miR-24 in B-cell lymphoma.Blood · 2024Article
- Sparse spectral graph analysis and its application to gastric cancer drug resistance-specific molecular interplays identification.PloS one · 2024Article
- NF-κB fingerprinting reveals heterogeneous NF-κB composition in diffuse large B-cell lymphoma.Frontiers in oncology · 2023Article
- Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study.Frontiers in genetics · 2023Article
- An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease.Frontiers in aging neuroscience · 2022Article
- Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19.International journal of molecular sciences · 2021Article
- Melatonin increases the chemosensitivity of diffuse large B-cell lymphoma cells to epirubicin by inhibiting P-glycoprotein expression via the NF-κB pathway.Translational oncology · 2021Article
- Clinical and Molecular Properties of Human Immunodeficiency Virus-Related Diffuse Large B-Cell Lymphoma.Frontiers in oncology · 2021Review
- Bioinformatics identification of CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment.Bioscience reports · 2020Article
- Article
- Review
- Effects of BTK signalling in pathogenic microorganism infections.Journal of cellular and molecular medicine · 2019Review
- The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers.Virologica Sinica · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epstein-Barr virus (EBV)-encoded nuclear antigen, EBNA2, expressed in EBV-infected B lymphocytes is critical for lymphoblastoid cell growth. Microarray profiling and cytokine array screening revealed that EBNA2 is associated with upregulation of the chemokines CCL3 and CCL4 in lymphoma cells. Depletion or inactivation of CCL3 or CCL4 sensitized DLBCL cells to doxorubicin. Our results indicate that EBV influences cell survival via an autocrine mechanism whereby EBNA2 increases CCL3 and CCL4, which in turn activate the Btk and NF-κB pathways, contributing to doxorubicin resistance of B lymphoma cells. Western blot data further confirmed that CCL3 and CCL4 direct activation of Btk and NF-κB. Based on these findings, we propose that a pathway involving EBNA2/Btk/NF-κB/CCL3/CCL4 plays a key role in doxorubicin resistance, and therefore, inhibition of specific components of this pathway may sensitize lymphoma cells to doxorubicin. Evaluation of the relationship between CCL3 expression and EBV infection revealed high CCL3 levels in EBV-positive patients. Our data collectively suggest that doxorubicin treatment for EBNA2-positive DLBCL cells may be effectively complemented with a NF-κB or Btk inhibitor. Moreover, evaluation of the CCL3 and CCL4 levels may be helpful for selecting DLBCL patients likely to benefit from doxorubicin treatment in combination with the velcade or ibrutinib.
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