Downregulation of STAT3 in EBV-positive Hodgkin lymphoma
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ABSTRACT:
PROVIDER: PRJNA842009 | ENA |
REPOSITORIES: ENA
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Project description:STAT3 encodes an oncogenic transcription factor which is activated via various signalling pathways or Epstein Barr virus (EBV)-infection. The tumor cells of Hodgkin lymphoma (HL) are derived from germinal center B-cells and transformed by chromosomal rearrangements, aberrant signal transduction, downregulation of transcription factors mediating B-cell differentiation, and EBV-infection. HL cell lines represent useful models to investigate the molecular pathology and deduced treatment options in this malignancy. Using cell line L-540, we have recently shown that constitutively activated STAT3 drives aberrant expression of hematopoietic NKL homeobox gene HLX. Here, we analyzed HL cell line AM-HLH which is EBV-positive but nevertheless HLX negative. Consistently, AM-HLH expressed decreased levels of STAT3 proteins which were additionally inactivated and located in the cytoplasm. Combined genomic and gene expression profiling data revealed amplified and overexpressed candidates involved in opposed regulation of STAT3 and EBV. Subsequent analyses demonstrated that IRF4 and NFATC inhibited STAT3 expression. However, treatment with IL6 or IL27 activated STAT3, elevated expression of HLX and MIR155, and inhibited IRF4. MIR155 (STAT3 target gene) and BCL11A and SPIB (target genes of HLX) are described as suppressors and activators of EBV and showed reduced and elevated expression levels in AM-HLH, respectively. Taken together, this cell line deals with two conflicting oncogenic drivers, namely JAK2-STAT3-signalling and EBV-infection but is sensitive to cytokine signalling, mediating a switch between these aberrant pathways. Thus, AM-HLH represents an interesting cell line model to study the pathogenic roles of STAT3 and EBV and their therapeutic implications in HL.
2022-12-31 | GSE204717 | GEO
Project description:STAT3 is a transcription factor which is activated via various signaling transduction pathways or Epstein-Barr virus (EBV) infection and plays an oncogenic role in lymphoid malignancies including Hodgkin lymphoma (HL). The tumor cells of HL are derived from germinal center B-cells and transformed by chromosomal rearrangements, aberrant signal transduction, deregulation of developmental transcription factors, and EBV activity. HL cell lines represent useful models to investigate molecular principles and deduced treatment options of this malignancy. Using cell line L-540, we have recently shown that constitutively activated STAT3 drives aberrant expression of hematopoietic NKL homeobox gene HLX. Here, we analyzed HL cell line AM-HLH which is EBV-positive but, nevertheless, HLX-negative. Consistently, AM-HLH expressed decreased levels of STAT3 proteins which were additionally inactivated and located in the cytoplasm. Combined genomic and expression profiling data revealed several amplified and overexpressed gene candidates involved in opposed regulation of STAT3 and EBV. Corresponding knockdown studies demonstrated that IRF4 and NFATC2 inhibited STAT3 expression. MIR155 (activated by STAT3) and SPIB (repressed by HLX) showed reduced and elevated expression levels in AM-HLH, respectively. However, treatment with IL6 or IL27 activated STAT3, elevated expression of HLX and MIR155, and inhibited IRF4. Taken together, this cell line deals with two conflicting oncogenic drivers, namely, JAK2-STAT3 signaling and EBV infection, but is sensitive to switch after cytokine stimulation. Thus, AM-HLH represents a unique cell line model to study the pathogenic roles of STAT3 and EBV and their therapeutic implications in HL.
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Project description:Epstein-Barr virus (EBV)- encoded RNAs (EBERs) are aboundance in all EBV lantency, it was found that EBERs may contribute to the oncogenesis. To study the role of EBV-encoded small RNAs (EBERs) in Hodgkin lymphoma, we transfected Hodgkin lymphoma cell lines, KMH2 and L428, with EBER1 and screen with microarrays to verify what is the possible role of the EBER1 in Hodgkin lymphoma.
2010-02-13 | GSE12427 | GEO
Project description:Nasal T/NK lymphoma is a unique subtype of non-Hodgkin lymphoma (NHL) that is aggressive and incurable closely associated with Epstein-Barr virus (EBV)3. The clonal expansion of EB infected T- or NK cell is also seen in patients with chronic active EBV (CAEBV) infection, suggesting that two diseases might partly share a similar mechanism by which EBV affect host cellular genes. In order to understand the pathogenesis of EBV-associated T/NK lymphoproliferative disorders (LPD) and design new therapies, we employed a novel EBV DNA microarray to compare patterns of EBV expression in SNK/T cells established from EBV-associated T/NK LPD. Keywords: parallel sample
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Project description:This SuperSeries is composed of the following subset Series: GSE25986: Gene expression profiling of cell lines derived from classical Hodgkin lymphoma GSE25987: Gene expression profiling of Hodgkin lymphoma cell line KMH2: Comparison of CIITA-BX648577 knockdown cultures with non-silencing controls GSE25989: Copy number analysis of Hodgkin lymphoma cell lines KM-H2 and L-428 Refer to individual Series *** This submission represents the microarray gene expression and microarray copy number components of the study
2010-12-11 | E-GEOD-25990 | biostudies-arrayexpress
Project description:Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FoxP3+ cells was higher in the microenvironment of EBV-related CHL, with P values of <0.001, <0.001 and <0.016, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated CHL cases (P < 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mechanisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.
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Project description:Whilst the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognized, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. We have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. Whilst loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. We investigated whether there were common gene expression changes between EBV-positive and loss clones derived for four endemic Burkitt lyphoma cell lines that could explain the apoptosis sensitivity of clones that had lost EBV.
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Project description:Global proteomics profiling of anaplastic large cell lymphoma cell lines DEL, SU-DHL-1 (ALK+), Mac-1, Mac-2A (ALK-) as well as Hodgkin lymphoma cell lines L-428, L-540, L-1236 and HDLM-2.
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Project description:While the Epstein-Barr virus (EBV) is known to drive de novo lymphomagenesis, it may rarely contribute to transformation of indolent lymphoma as well. Some EBV-related lymphomas represent a diagnostic challenge with important prognostic and therapeutic implications. We describe a case of follicular lymphoma (FL) transformation to both EBV + diffuse large B-cell lymphoma (DLBCL) and EBV + classic Hodgkin lymphoma (cHL), the latter of which was only identified retrospectively after selective outgrowth during DLBCL therapy. Finally, we describe successful salvage therapy with brentuximab vedotin plus nivolumab. This is the first known case of composite lymphoma with FL, EBV + DLBCL, and EBV + cHL within a single lymph node. The disease course highlights the importance of careful morphologic examination and comprehensive immunophenotypic characterization of EBV + lymphomas to ensure proper clinical care and underscores the potential for novel therapies currently under investigation. This trial is registered with NCT01671813.
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Project description:Genomewide gene expression analysis of lymphoid cell lines of Hodgkin, non-Hodgkin and acute leukemia origin
2010-11-17 | GSE20011 | GEO