Hodgkin Lymphoma

2018 ◽  
Author(s):  
Henrik Hjalgrim ◽  
Mads Melbye ◽  
Pagona Lagiou
Keyword(s):  
Natural History ◽  
Hodgkin Lymphoma ◽  
Cell Transformation ◽  
Malignant Cell ◽  
Future Research ◽  
Barr Virus ◽  
History Of ◽  
Epstein Barr ◽  
Malignant Cell Transformation

The descriptive epidemiology of Hodgkin lymphoma (HL) has demonstrated marked variation by age, sex, social class, and time, strongly suggesting both a role of environmental factors and the existence of etiologically diverse HL subtypes. There is increasing evidence that Epstein Barr virus (EBV)–positive and EBV-negative classical HLs define two variants with separate etiologies. The risk for both increases with family history, whereas immune dysfunction and infectious mononucleosis have been implicated in EBV-positive HL risk only. Despite being the less common of the two, the natural history of EBV-positive HL is currently the best understood, both with respect to how EBV may contribute to malignant cell transformation and in relation to constitutional and environmental risk factors. Meanwhile, the understanding of the natural history of EBV-negative HL is meager. Future research for EBV-negative HL is expected to focus on its presumed infectious etiology, for which there are currently no strong candidates.

scholarly journals Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma

2020 ◽  
Vol 117 (46) ◽  
pp. 28980-28991
Author(s):  
Zhihui Song ◽  
Wei Wei ◽  
Wenming Xiao ◽  
Essel D. Al-Saleem ◽  
Reza Nejati ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Strong Support ◽  
Ubiquitin Chain ◽  
Guide Rna ◽  
Barr Virus ◽  
Protein Ubiquitination ◽  
Crispr Screen ◽  
Epstein Barr

More than 70% of Epstein–Barr virus (EBV)-negative Hodgkin lymphoma (HL) cases display inactivation of TNFAIP3 (A20), a ubiquitin-editing protein that regulates nonproteolytic protein ubiquitination, indicating the significance of protein ubiquitination in HL pathogenesis. However, the precise mechanistic roles of A20 and the ubiquitination system remain largely unknown in this disease. Here, we performed high-throughput CRISPR screening using a ubiquitin regulator-focused single-guide RNA library in HL lines carrying either wild-type or mutant A20. Our CRISPR screening highlights the essential oncogenic role of the linear ubiquitin chain assembly complex (LUBAC) in HL lines, which overlaps with A20 inactivation status. Mechanistically, LUBAC promotes IKK/NF-κB activity and NEMO linear ubiquitination in A20 mutant HL cells, which is required for prosurvival genes and immunosuppressive molecule expression. As a tumor suppressor, A20 directly inhibits IKK activation and HL cell survival via its C-terminal linear-ubiquitin binding ZF7. Clinically, LUBAC activity is consistently elevated in most primary HL cases, and this is correlated with high NF-κB activity and low A20 expression. To further understand the complete mechanism of NF-κB activation in A20 mutant HL, we performed a specifically designed CD83-based NF-κB CRISPR screen which led us to identify TAK1 kinase as a major mediator for NF-κB activation in cells dependent on LUBAC, where the LUBAC-A20 axis regulates TAK1 and IKK complex formation. Finally, TAK1 inhibitor Takinib shows promising activity against HL in vitro and in a xenograft mouse model. Altogether, these findings provide strong support that targeting LUBAC or TAK1 could be attractive therapeutic strategies in A20 mutant HL.

scholarly journals miRNAs: EBV Mechanism for Escaping Host’s Immune Response and Supporting Tumorigenesis

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 353 ◽  
Author(s):  
Snježana Židovec Lepej ◽  
Maja Matulić ◽  
Paula Gršković ◽  
Mirjana Pavlica ◽  
Leona Radmanić ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Cell Transformation ◽  
Regulation Of Gene Expression ◽  
Cell Communication ◽  
Human Herpesvirus ◽  
Human Virus ◽  
Barr Virus ◽  
Epstein Barr

Epstein-Barr virus (EBV) or human herpesvirus 4 (HHV-4) is a ubiquitous human oncogenic virus, and the first human virus found to express microRNAs (miRNAs). Its genome contains two regions encoding more than 40 miRNAs that regulate expression of both viral and human genes. There are numerous evidences that EBV miRNAs impact immune response, affect antigen presentation and recognition, change T- and B-cell communication, drive antibody production during infection, and have a role in cell apoptosis. Moreover, the ability of EBV to induce B-cell transformation and take part in mechanisms of oncogenesis in humans is well known. Although EBV infection is associated with development of various diseases, the role of its miRNAs is still not understood. There is abundant data describing EBV miRNAs in nasopharyngeal carcinoma and several studies that have tried to evaluate their role in gastric carcinoma and lymphoma. This review aims to summarize so far known data about the role of EBV miRNAs in altered regulation of gene expression in human cells in EBV-associated diseases.

NATURAL HISTORY OF THE AIDS RELATED COMPLEX IN HEMOPHILIA—RELATIONSHIPS TO EPSTEIN BARR VIRUS

Aids Research ◽  
1983 ◽  
Vol 1 (3) ◽  
pp. 197-209 ◽  
Author(s):  
Francine Gervais ◽  
Christos Tsoukas ◽  
Abraham Fuks ◽  
Joseph Shuster
Keyword(s):  
Natural History ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Aids Related Complex ◽  
History Of ◽  
Epstein Barr ◽  
Related Complex

MUC1 Story: Great Expectations, Disappointments and the Renaissance

2019 ◽  
Vol 26 (3) ◽  
pp. 554-563 ◽  
Author(s):  
Marina S. Syrkina ◽  
Yegor S. Vassetzky ◽  
Mikhail A. Rubtsov
Keyword(s):  
Cell Transformation ◽  
Therapeutic Potential ◽  
Practical Importance ◽  
Anticancer Therapy ◽  
Malignant Cell ◽  
Great Expectations ◽  
Tumor Dissemination ◽  
History Of ◽  
Malignant Cell Transformation ◽  
Strong Ground

In the course of studying human mucin MUC1, the attitude towards this molecule has been changing time and again. Initially, the list of presumable functions of MUC1 was restricted to protecting and lubricating epithelium. To date, it is assumed to play an important role in cell signaling as well as in all stages of oncogenesis, from malignant cell transformation to tumor dissemination. The story of MUC1 is full of hopes and disappointments. However, the scientific interest to MUC1 has never waned, and the more profoundly it has been investigated, the clearer its hidden potential turned to be disclosed. The therapeutic potential of mucin MUC1 has already been noted by various scientific groups at the early stages of research. Over forty years ago, the first insights into MUC1 functions became a strong ground for considering this molecule as potential target for anticancer therapy. Therefore, this direction of research has always been of particular interest and practical importance. More than 200 papers on MUC1 were published in 2016; the majority of them are dedicated to MUC1-related anticancer diagnostics and therapeutics. Here we review the history of MUC1 studies from the very first attempts to reveal its functions to the ongoing renaissance.

scholarly journals The Role of Epstein-Barr Virus LMP-1 Immunohistochemical Staining in Childhood Hodgkin Lymphoma

2015 ◽  
Vol 25 (6) ◽  
Author(s):  
Hikmet Gulsah Tanyildiz ◽  
Inci Yildiz ◽  
Nuray Bassullu ◽  
Nukhet Tuzuner ◽  
Alp Ozkan ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Immunohistochemical Staining ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Epstein Barr Virus in childhood and adolescent classical Hodgkin lymphoma in a French cohort of 301 patients

2021 ◽  
Author(s):  
Victor Pereira ◽  
Sabah Boudjemaa ◽  
Caroline Besson ◽  
Thierry Leblanc ◽  
Charlotte Rigaud ◽  
...  
Keyword(s):  
Viral Load ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Male Gender ◽  
Barr Virus ◽  
Classic Hodgkin Lymphoma ◽  
Male Patients ◽  
Epstein Barr

To analyze the role of Epstein-Barr virus (EBV) in the biological and clinical characteristics of patients treated for classic Hodgkin lymphoma (cHL) in France. Bio-pathological data of 301 patients treated for a cHL in or according to the protocol of the EuroNet PHL-C1 trial between November 2008 and February 2013 were centrally reviewed. Median age at diagnosis was 14 [3-18] years and the F/M ratio 0.86, 0.47 before 10 years and 0.9 from 11 to 18. CHL subtypes were nodular sclerosis for 266/301 (88%) patients, mixed cellularity for 22/301 (7%), lymphocyte rich for 2/301 (1%), and 11/301 were unclassified. EBV expression in situ (EBV cHL) was observed for 68/301 (23%) patients, significantly associated with MC subtype and male gender, and there was a trend with age <10 years, it was particularly overrepresented in boys below 10 years: 15/23 (65%) vs 28/139 among other male patients (20%). Event-free and overall survival were equivalent between EBV and non-EBV cHL patients. EBV viral load was tested for 108/301 patients and detectable in 22/108 (22%) cases. A positive viral load was overrepresented in EBV cHL versus non-EBV cHL patients: 13/28 (46%) vs 9/80 (11%). Detailed semi-quantitative histological analysis showed a high number of B-cell residual follicles in EBV cHL and no significant association with CD 20 or PAX 5 immunostaining in tumoral cells relative to EBV-negative HL. Distribution of EBV cHL in children and adolescents is associated with young age and male gender, suggesting a specific physiopathology and may require a differential therapeutic approach.

scholarly journals An etiological role for the Epstein-Barr virus in the pathogenesis of classical Hodgkin lymphoma

Blood ◽  
2019 ◽  
Vol 134 (7) ◽  
pp. 591-596 ◽  
Author(s):  
Paul G. Murray ◽  
Lawrence S. Young
Keyword(s):  
Small Molecules ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Classical Hodgkin Lymphoma ◽  
Pathogenic Role ◽  
Chl A ◽  
Barr Virus ◽  
Recent Developments ◽  
Epstein Barr

Abstract Although a pathogenic role for the Epstein-Barr virus (EBV) is largely undisputed for tumors that are consistently EBV genome positive (eg, nasopharyngeal carcinoma, endemic Burkitt lymphoma), this is not the case for classical Hodgkin lymphoma (cHL), a tumor with only a variable EBV association. In light of recent developments in immunotherapeutics and small molecules targeting EBV, we believe it is now timely to reevaluate the role of EBV in cHL pathogenesis.

scholarly journals Th17 immune microenvironment in Epstein-Barr virus–negative Hodgkin lymphoma: implications for immunotherapy

2017 ◽  
Vol 1 (17) ◽  
pp. 1324-1334 ◽  
Author(s):  
Amy S. Duffield ◽  
Maria Libera Ascierto ◽  
Robert A. Anders ◽  
Janis M. Taube ◽  
Alan K. Meeker ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Immune Microenvironment ◽  
Barr Virus ◽  
Key Points ◽  
Epstein Barr

Key Points CHL broadly expresses the PD-1/PD-L1 pathway, but EBV+ CHL displays a Th1 profile, whereas EBV− tumors have a pathogenic Th17 profile. These findings support further studies to define the role of the IL-23/IL-17 axis in CHL response/resistance to anti-PD-1 therapy.

scholarly journals RETRACTED ARTICLE: Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Poyil Pratheeshkumar ◽  
Young-Ok Son ◽  
Sasidharan Padmaja Divya ◽  
Lei Wang ◽  
Zhuo Zhang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Cell Transformation ◽  
Arsenic Exposure ◽  
Malignant Cell ◽  
Bronchial Epithelial ◽  
Signaling Axis ◽  
Retracted Article ◽  
Programmed Cell Death 4 ◽  
Malignant Cell Transformation

Abstract Arsenic is a well-documented human carcinogen. The present study explored the role of the onco-miR, miR-21 and its target protein, programmed cell death 4 (PDCD4) in arsenic induced malignant cell transformation and tumorigenesis. Our results showed that treatment of human bronchial epithelial (BEAS-2B) cells with arsenic induces ROS through p47phox, one of the NOX subunits that is the key source of arsenic-induced ROS. Arsenic exposure induced an upregulation of miR-21 expression associated with inhibition of PDCD4, and caused malignant cell transformation and tumorigenesis of BEAS-2B cells. Indispensably, STAT3 transcriptional activation by IL-6 is crucial for the arsenic induced miR-21 increase. Upregulated miR-21 levels and suppressed PDCD4 expression was also observed in xenograft tumors generated with chronic arsenic exposed BEAS-2B cells. Stable shut down of miR-21, p47phox or STAT3 and overexpression of PDCD4 or catalase in BEAS-2B cells markedly inhibited the arsenic induced malignant transformation and tumorigenesis. Similarly, silencing of miR-21 or STAT3 and forced expression of PDCD4 in arsenic transformed cells (AsT) also inhibited cell proliferation and tumorigenesis. Furthermore, arsenic suppressed the downstream protein E-cadherin expression and induced β-catenin/TCF-dependent transcription of uPAR and c-Myc. These results indicate that the ROS-STAT3-miR-21-PDCD4 signaling axis plays an important role in arsenic -induced carcinogenesis.

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