ReviewCancer science2007
Pathogenesis and mechanism of disease progression from hemophagocytic lymphohistiocytosis to Epstein-Barr virus-associated T-cell lymphoma: nuclear factor-kappa B pathway as a potential therapeutic target.
Review in Cancer science, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 94 citations in OpenAlex.
- Ruxolitinib Penetrates Blood Brain Barrier and Reduces the Cytokine Storm in Patients With Haemophagocytic Lymphohistiocytosis.Journal of cellular and molecular medicine · 2026Article
- Natural Killer/T-Cell Lymphoma-Associated Hemophagocytic lymphohistiocytosis-a Rare and Dangerous Disease.Blood and lymphatic cancer : targets and therapy · 2026Review
- Case Report: Two cases of chronic active Epstein-Barr virus disease presenting as refractory sinusitis.Frontiers in immunology · 2025Article
- Significance of whole-blood EBV DNA status in T/NK-cell lymphoma-associated hemophagocytic lymphohistiocytosis: a single-center retrospective analysis.Therapeutic advances in hematology · 2025Article
- Brain MRI imaging markers associated with death in children with central nervous system involvement of hemophagocytic lymphohistiocytosis.European radiology · 2024Article
- Laboratory Features and Pathology of Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- The emerging role of anti-PD-1 antibody-based regimens in the treatment of extranodal NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis.Journal of cancer research and clinical oncology · 2023Article
- Matrin3 (MATR3) Expression Is Associated with Hemophagocytosis.Biomedicines · 2022Article
- Immunosuppressive Tumor Microenvironment and Immunotherapy of Epstein-Barr Virus-Associated Malignancies.Viruses · 2022Review
- Update on Molecular Diagnosis in Extranodal NK/T-Cell Lymphoma and Its Role in the Era of Personalized Medicine.Diagnostics (Basel, Switzerland) · 2022Review
- F-18 FDG PET/CT in NK/T-Cell Lymphoma that Progressed from Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis.Nuclear medicine and molecular imaging · 2022Article
- Immune cartography of macrophage activation syndrome in the COVID-19 era.Nature reviews. Rheumatology · 2021Review
- Hemophagocytic lymphohistiocytosis is associated with Bartonella henselae infection in a patient with multiple susceptibility genes.Annals of clinical microbiology and antimicrobials · 2020Article
- Central Nervous System Involvement in 179 Chinese Children with Hemophagocytic Lymphohistiocytosis.Chinese medical journal · 2018Article
- Lymphoma associated hemophagocytic syndrome: A single-center retrospective study.Oncology letters · 2018Article
- Proliferation through activation: hemophagocytic lymphohistiocytosis in hematologic malignancy.Blood advances · 2017Review
- Post-cytokine-release Salt Wasting as Inverse Tumor Lysis Syndrome in a Non-cerebral Natural Killer-cell Neoplasm.Internal medicine (Tokyo, Japan) · 2017Article
- Article
- Haemophagocytic lymphohistiocytosis in inflammatory bowel disease with virus infection.Przeglad gastroenterologiczny · 2015Review
- Natural killer/T-cell lymphoma-associated hemophagocytic syndrome: A case report.Oncology letters · 2014Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epstein-Barr virus (EBV) can infect T lymphocytes and manifests as hemophagocytic lymphohistiocytosis (HLH), a distinct entity of hemophagocytic syndrome (HPS) characterized by fever, hepatosplenomegaly, cytopenia, hypercytokinemia, and systemic macrophage activation with hemophagocytosis. In a substantial percentage of HLH patients, the disease may relapse or progress to T-cell lymphoma in months to years. In the present review, the authors summarize the previous studies on the pathogenesis of HLH and the potential mechanism for the progression of disease from HLH to T-cell lymphoma. The infection of T cells by EBV could activate T cells to secrete proinflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), which subsequently activate macrophages. EBV latent membrane protein-1 (LMP-1) is the viral product responsible for the activation of the TNF receptor (TNFR) associated factors/nuclear factor-kappaB (NF-kappaB)/ERK pathway to enhance cytokine secretion mediated through the suppression of the SAP/SH2D1A gene. The activation of NF-kappaB will confer resistance to TNF-alpha-induced apoptosis on EBV-infected T cells through the down-regulation of TNFR-1. Consistent with in vitro observations, EBV-associated T or natural killer/T-cell lymphoma showed constitutive activation of NF-kappaB, explaining its drug resistance, hypercytokinemia, and poor prognosis. Therefore, similar to other inflammation-associated cancers, HLH provides a unique model to study the mechanism of disease progression from a benign virus-infected disorder (HLH) to T-cell lymphoma. Inhibition of the NF-kappaB signal pathway should provide a potential target for the treatment of HLH and EBV-associated T-cell lymphoma.
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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.