EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis

Liu, Ting-Yun; Wu, Shang‐Ju; Huang, Mi-Hsin; Lo, Fei-Yun; Tsai, Mong‐Hsun; Tsai, Ching-Hwa; Hsu, Su-Ming; Lin, Chung-Wu

doi:10.1186/1476-4598-9-32

Cited by 18 publications

(14 citation statements)

References 43 publications

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“…The present data show comparable p53 induction following docetaxel treatment in the two cell lines, while p21 expression was lower in EBV-positive GC than in EBV-negative GC. In EBV-positive Hodgkin's lymphoma, the expressions of p21 and caspase-3 were shown to be lower than in EBV-negative Hodgkin's lymphoma due to EBER1 function, which resulted in decreased cell death (Liu et al, 2010). Thus, it is possibile that in EBV-positive GC cells, suppressed p21 expression by EBER1 might cause chemoresistance.…”

Section: Discussionmentioning

confidence: 98%

Association between Epstein-Barr Virus Infection and Chemoresistance to Docetaxel in Gastric Carcinoma

Shin

Kim

Lee

2011

Molecules and Cells

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Epstein-Barr virus (EBV) is associated with human cancers such as nasopharyngeal carcinoma, Burkitt's lymphoma, Hodgkin's disease, and gastric carcinoma (GC). EBV is associated with about 10% of all GC cases globally. EBV-associated GC has distinct features from EBV-negative GC. However, it is still unclear if EBV infection has any effect on GC chemoresistance. Cell proliferation assay, cell cycle analysis, and active caspase Western blot revealed that the EBV-positive GC cell line (AGS-EBV) showed chemoresistance to docetaxel compared to the EBV-negative GC cell line (AGS). Docetaxel treatment increased expression of Bax similarly in AGS and AGS-EBV cell lines. However, Bcl-2 induction was markedly higher in AGS-EBV cells, after docetaxel treatment. Although docetaxel increased the expression of p53 to a similar extent in both cell lines, induction of p21 in AGS-EBV cells was lower than in AGS cells. Furthermore, expression of survivin was higher in AGS-EBV cells than in AGS cells following docetaxel treatment as well as at basal state. EBVlytic gene expression was induced by docetaxel treatment in AGS-EBV cells. The results suggest that EBV infection and lytic induction confers chemoresistance to GC, possibly by regulating cellular and EBV latent and lytic gene expression.

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Section: Discussionmentioning

confidence: 98%

Association between Epstein-Barr Virus Infection and Chemoresistance to Docetaxel in Gastric Carcinoma

Shin

Kim

Lee

2011

Molecules and Cells

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“…LMP‐1 and LMP‐2 may also contribute to the reprogramming of the B cell phenotype that occurs in HRS cells; 125,126 in particular, LMP‐2 constitutively activates the Notch pathway leading to alteration of levels of the transcription factors E2A and EBF (see above). The non‐coding EBER RNAs have been shown to suppress p21cip/waf transcription, thereby increasing apoptosis resistance through down‐regulation of p53, EGR1 and STAT1 127 . The BARTs are a group of alternatively spliced RNAs derived from the Bam HI A fragment of the EBV genome, which encode a large number of microRNAs.…”

Section: Ebv and Hlmentioning

confidence: 99%

The molecular pathogenesis of Hodgkin lymphoma

Farrell

Jarrett

2011

Histopathology

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Farrell K & Jarrett R F (2011) Histopathology 58, 15–25 The molecular pathogenesis of Hodgkin lymphoma Hodgkin lymphoma (HL) is an unusual malignancy in that the tumour cells, the Hodgkin and Reed–Sternberg (HRS) cells, are a minor component of the tumour mass, the bulk of which is a mixed cellular infiltrate. There is compelling evidence that HRS cells are clonal B cells that have lost their B cell phenotype. Mature B cells lacking B cell receptors would normally die by apoptosis, and therefore HRS cells must have developed mechanisms to facilitate survival. The escape from apoptosis and transcriptional reprogramming of HRS cells are interlinked and appear central to disease pathogenesis. Epstein–Barr virus (EBV) is present in the HRS cells of a proportion of cases and expresses genes with a plausible oncogenic function. It is likely that EBV plays a role in reprogramming and survival through dysregulation of several signalling networks and transcription factors, including nuclear factor (NF)‐κB. Activation of NF‐κB is a feature of all HRS cells and gene mutations affecting this pathway appear common in EBV‐negative HL. The HRS cell furthers its own survival by attracting a supportive microenvironment of immune and stromal cells, and suppressing local immune responsiveness. Although many questions remain unanswered, the last two decades have witnessed a considerable increase in our knowledge of this complex disease.

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“…Because these drugs were known to act by increasing p21 cip1/waf1 , the anti-apoptotic activity of EBER1 was probably through the suppression of p21 cip1/waf1 . Clinically, EBV-related HL had weaker expression of p21 cip1/waf1 and a worse prognosis, which also supported a critical role of EBER1 in the rescue of Reed-Sternberg cells from apoptosis and in the clinical behaviors of HLs [28]. The frequency of genetic lesions or viral infections that affect the activity of the NF-κB pathway and the STAT pathway in HRS cells is varied.…”

Section: Discussionmentioning

confidence: 81%

CD30 expression and Detection of Epstein-Barr Virus-Encoded Small RNA by Real-Time RT-PCR of Classic Hodgkin Lymphoma and Their Correlation with Risk Stratification

Nurusshofa

Suryanti

Afiati

et al. 2019

ijmsci

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More than 40% patient of Hodgkin lymphoma (HL) are chemoresistance and show early disease relapse that leads to poor prognostic. Epstein-Barr Virus (EBV) appears to have poor prognostic in HL. The CD30 expression at Hodgkin and Reed-Stenberg cells suggested has associated with advanced disease stage. The International Prognostic Score-7 (IPS) is a seven-parameter of risk stratification index for prognostic and as a consideration for treatment plan. The aim of this journal is to see correlation between EBV infection and CD30 expression with IPS-7 in Classic HL (CHL) patient. Case-control research design was done to 40 Fixed Formalin Paraffin-Embedded (FFPE) of CHL at the Dr Hasan Sadikin Hospital, Bandung. Cases were 20 patients CHL of high-risk score IPS-7 and controls were 20 patients with low-risk score. Detection of EBV-encoded small RNA-1 (EBER1) by Real-Time RT-PCR and Immunohistochemical staining of CD30 was performed to all samples. All data were analyzed using Chi-Square test with p-value <0.05 of significant level. EBV was present in 10 cases of CHL (25%). The result of this study shows a different statistically significant of EBV infection (p=0.028) and CD30 expression (p=0.004) between low risk and high-risk IPS-7 HL. CD30 expression (OR= 7.429) may provide stronger factor for risk assessment for the patient with HL, compare to EBER1 detection (OR=6.000). This study concluded that CD30 expression and EBV Infection correlate with risk assessment IPS-7 in CHL.

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EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis

Cited by 18 publications

References 43 publications

Association between Epstein-Barr Virus Infection and Chemoresistance to Docetaxel in Gastric Carcinoma

Association between Epstein-Barr Virus Infection and Chemoresistance to Docetaxel in Gastric Carcinoma

The molecular pathogenesis of Hodgkin lymphoma

CD30 expression and Detection of Epstein-Barr Virus-Encoded Small RNA by Real-Time RT-PCR of Classic Hodgkin Lymphoma and Their Correlation with Risk Stratification

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