ArticlePloS one2019
Epstein-Barr virus (EBV) activates NKL homeobox gene HLX in DLBCL.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Epstein-Barr virus-associated lymphoma: current understanding and treatment strategies.Blood research · 2026Review
- Tumor-Associated Sympathetic Nerves Promote the Progression of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oncoviruses in the Oral Cavity: Recent Advances in Understanding Viral Infections and Tumorigenesis.International journal of molecular sciences · 2025Review
- Single-cell transcriptomics of melanoma sentinel lymph nodes identifies immune cell signatures associated with metastasis.JCI insight · 2025Article
- Epstein-Barr virus: the mastermind of immune chaos.Frontiers in immunology · 2024Review
- EBV and Lymphomagenesis.Cancers · 2023Review
- The Potential Dual Role of H2.0-like Homeobox in the Tumorgenesis and Development of Colorectal Cancer and Its Prognostic Value.Canadian journal of gastroenterology & hepatology · 2023Article
- Downregulation of STAT3 in Epstein-Barr Virus-Positive Hodgkin Lymphoma.Biomedicines · 2022Article
- The Role of NKL Homeobox Genes in T-Cell Malignancies.Biomedicines · 2021Review
- Molecular Interactions between Two LMP2A PY Motifs of EBV and WW Domains of E3 Ubiquitin Ligase AIP4.Life (Basel, Switzerland) · 2021Article
- NKL-Code in Normal and Aberrant Hematopoiesis.Cancers · 2021Review
- Signaling pathways of EBV-induced oncogenesis.Cancer cell international · 2021Review
- Establishment of the TBX-code reveals aberrantly activated T-box gene TBX3 in Hodgkin lymphoma.PloS one · 2021Article
- Establishment of the TALE-code reveals aberrantly activated homeobox gene PBX1 in Hodgkin lymphoma.PloS one · 2021Article
- The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in anaplastic large cell lymphoma (ALCL).Oncotarget · 2020Article
- Identification of lncRNAs Involved in PCV2 Infection of PK-15 Cells.Pathogens (Basel, Switzerland) · 2020Article
- Deregulated NKL Homeobox Genes in B-Cell Lymphoma.Cancers · 2019Review
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NKL homeobox genes encode developmental transcription factors regulating basic processes in cell differentiation. According to their physiological expression pattern in early hematopoiesis and lymphopoiesis, particular members of this homeobox gene subclass constitute an NKL-code. B-cell specific NKL-code genes generate a regulatory network and their deregulation is implicated in B-cell lymphomagenesis. Epstein-Barr virus (EBV) infects B-cells and influences the activity of signalling pathways including JAK/STAT and several genes encoding developmental regulators. Therefore, EBV-infection impacts the pathogenesis and the outcome of B-cell malignancies including Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL). Here, we isolated EBV-positive and EBV-negative subclones from the DLBCL derived cell line DOHH-2. These subclones served as models to investigate the role of EBV in deregulation of the B-cell specific NKL-code members HHEX, HLX, MSX1 and NKX6-3. We showed that the EBV-encoded factors LMP1 and LMP2A activated the expression of HLX via STAT3. HLX in turn repressed NKX6-3, SPIB and IL4R which normally mediate plasma cell differentiation. In addition, HLX repressed the pro-apoptotic factor BCL2L11/BIM and hence supported cell survival. Thus, EBV aberrantly activated HLX in DLBCL, thereby disturbing both B-cell differentiation and apoptosis. The results of our study appreciate the pathogenic role of EBV in NKL homeobox gene deregulation and B-cell malignancies.
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