scholarly journals Kaposi’s Sarcoma-Associated Virus Governs Gene Expression Profiles Toward B Cell Transformation

Author(s):  
Keiji Ueda ◽  
Emi Ito ◽  
Masato Karayama ◽  
Eriko Ohsaki ◽  
Kazushi Nakano ◽  
...  
2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Keiji Ueda ◽  
Eriko Ohsaki ◽  
Kazushi Nakano ◽  
Xin Zheng

Among herpesviruses, γ-herpesviruses are supposed to have typical oncogenic activities. Two human γ-herpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), are putative etiologic agents for Burkitt lymphoma, nasopharyngeal carcinoma, and some cases of gastric cancers, and Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma (PEL) especially in AIDS setting for the latter case, respectively. Since such two viruses mentioned above are highly species specific, it has been quite difficult to prove their oncogenic activities in animal models. Nevertheless, the viral oncogenesis is epidemiologically and/or in vitro experimentally evident. This time, we investigated gene expression profiles of KSHV-oriented lymphoma cell lines, EBV-oriented lymphoma cell lines, and T-cell leukemia cell lines. Both KSHV and EBV cause a B-cell-originated lymphoma, but the gene expression profiles were typically classified. Furthermore, KSHV could govern gene expression profiles, although PELs are usually coinfected with KSHV and EBV.


Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2285-2290 ◽  
Author(s):  
James Z. Huang ◽  
Warren G. Sanger ◽  
Timothy C. Greiner ◽  
Louis M. Staudt ◽  
Dennis D. Weisenburger ◽  
...  

Recently we have identified subgroups of de novo primary diffuse large B-cell lymphoma (DLBCL) based on complementary DNA microarray-generated gene expression profiles. To correlate the gene expression profiles with cytogenetic abnormalities in these DLBCLs, we examined the occurrence of the t(14;18)(q32;q21) in the 2 distinctive subgroups of DLBCL: one with the germinal center B-cell gene expression signature and the other with the activated B cell–like gene expression signature. The t(14;18) was detected in 7 of 35 cases (20%). All 7 t(14;18)-positive cases had a germinal center B-cell gene expression profile, representing 35% of the cases in this subgroup, and 6 of these 7 cases had very similar gene expression profiles. The expression of bcl-2 and bcl-6 proteins was not significantly different between the t(14;18)-positive and -negative cases, whereas CD10 was detected only in the group with the germinal center B-cell expression profile, and CD10 was most frequently expressed in the t(14;18)-positive cases. This study supports the validity of subdividing DLBCL into 2 major subgroups by gene expression profiling, with the t(14;18) being an important event in the pathogenesis of a subset of DLBCL arising from germinal center B cells. CD10 protein expression is useful in identifying cases of DLBCL with a germinal center B-cell gene expression profile and is often expressed in cases with the t(14;18).


Oncology ◽  
2008 ◽  
Vol 75 (1-2) ◽  
pp. 71-80 ◽  
Author(s):  
Zeenath Jehan ◽  
Abdul K. Siraj ◽  
Jehad Abubaker ◽  
Christian Ruiz ◽  
Ronald Simon ◽  
...  

2019 ◽  
Vol 26 (5) ◽  
pp. 348-356
Author(s):  
Xiu Li Feng ◽  
Yang Zheng ◽  
Shan Shan Hao ◽  
Guang Fang Zhou ◽  
Pu Yan Chen

Background: The Bursa of Fabricius is an acknowledged central humoral immune organ unique to birds, which provides an ideal research model on the immature B cell development. Objective: In this article, our motivation is to study the role on sIgM and establish the molecular basis and functional processes of Bursal Hexapeptide (BHP) in avian immature B cells DT40 cell lines. Methods: In this article, we detected the expressions of sIgM mRNA with qPCR in DT40 cells with BHP treatment, and investigated the gene expression profiles of BHP-treated DT40 cells, employing microarray analyses. Also, to validate the differentially expressed genes, we performed KEGG pathway and Gene Ontology analysis in the BHP-treated DT40 cells. Finally, we comparatively analyzed the similar regulated genes and their involved immune functional processes between DT40 cell and mouse immature B cell line WEHI231 cell with BHP treatment. Results: Following the proposed framework, we proved that the BHP enhanced the mRNA expression levels of IgM in DT40 cells, and induced 460 upregulated genes and 460 downregulated genes in BHP-treated DT40 cells. The pathway analysis showed that the differentially regulated genes in DT40 cell line with BHP treatment were involved in 12 enrichment pathways, in which Toll-like receptor signaling pathway was the vital pathways, and cytokine-cytokine receptor interaction and Jak-STAT signaling pathway were another two important pathways in BHP-treated DT40 cells. Moreover, BHP induced the immune related biological processes in BHP-treated DT40 cells, including T cell related, cytokine related, lymphocyte related, and innate immune response GO terms. Finally, the comparatively analysis showed that there were two downregulated genes GATA3 and IFNG to be found co-existed among the differentially expressed genes in BHP-treated DT40 cell and WEHI231 cells, which shared some same immune related functional processes in both cell lines. Conclusion: After the applying the framework, we proved the inducing roles and the gene expression profiles of BHP on avian immature B cells, and verified some molecular basis from the KEGG and GO analysis. These results provided the insight for mechanism on immature B cell differentiation, and offer the essential direction for the vaccine improvement.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3730-3730 ◽  
Author(s):  
Jason L. Smith ◽  
Amee Patel ◽  
Siyao Fan ◽  
Cassandra L. Jacobs ◽  
Katherine J. Walsh ◽  
...  

Abstract Abstract 3730 Poster Board III-666 Background Histone deacetylase (HDAC) inhibition has emerged as a promising therapeutic approach in malignancies. HDAC inhibition has proved to be a particularly effective option in patients with lymphoma. The HDAC inhibitor vorinostat is approved for the treatment of patients with cutaneous T-cell lymphomas and is being tested in patients with B cell lymphomas. More recently, a number of other HDAC inhibitors have entered preclinical and clinical testing. The mechanisms through which HDAC inhibitors exert their downstream effects are currently unknown. As the number of HDAC inhibitors in development increases, it is unclear if they share a class effect or display unique mechanisms of action. Recently, LBH589 has been described as an orally available, highly potent inhibitor of HDAC. We decided to explore whether LBH589 would be an effective therapeutic option for patients with lymphoma. Methods and Results In order to evaluate whether LBH was efficacious and potent in B cell lymphomas, we tested both vorinostat and LBH589 in the same cell line(s). We found that LBH589 was over 10 times more potent than vorinostat (mean IC50 7.4nM versus 830nM). We decided to further test LBH589 in an expanded panel of 18 cell lines derived from 5 different lymphoid malignancies: Burkitt lymphoma, mantle cell lymphoma, Hodgkin lymphoma, multiple myeloma and diffuse large B cell lymphoma. LBH589 was found to be lethal in each of these cell lines at IC50 concentrations varying from 5.6-31.5 nM (mean 11.2nM), suggesting that this drug may be effective at physiologically achievable concentrations. Based on the IC50 cut-off of 10nM, we assigned the treated cell lines to 2 groups: highly sensitive (IC50 < 10nM, N=11) and less sensitive (IC50> 10nM, N=8). We performed gene expression profiling on 12 of these cell lines and compared the gene expression profiles of the highly sensitive versus less sensitive cell lines. Further, we performed time course experiments in which we evaluated the effects of LBH589 at its IC50 on cell lines at 6 and 12 hours post-treatment. Gene expression profiling was performed on the treated cells at each time point. We also engineered resistant cell lines by incremental dose escalation over a period of months to a concentration greater than or equal to the IC50. The resistant cell lines were also profiled for gene expression and compared to the wild type cell lines. The gene expression profiles of LBH589 treated cells at 6 and 12 hours demonstrated a clear and progressive down regulation of genes associated with the NF-KB pathway (Figure 1). Furthermore, cell lines with high expression of genes in the NF-KB pathway were uniformly highly sensitive to LBH589 with IC50<10nM in all cases. Conclusion NF-KB activation is a common feature of many different lymphoma types. Our data suggest that HDAC inhibition using LBH589 could provide a potent method for treating lymphomas and that HDAC inhibitors may exert their effects through the down-regulation of the NF-KB pathway. Our data also suggest a rationale for dual inhibition of HDAC and NF-KB in the treatment of lymphoma. Disclosures: Rizzieri: Merck & Co., Inc.: Consultancy.


2018 ◽  
Vol 140 (2) ◽  
pp. 87-96
Author(s):  
Haitao Xu ◽  
Fusheng Yao

Waldenström macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is rare but a clinicopathologically distinct B-cell malignancy. This study assessed differentially expressed genes (DEGs) to identify potential WM biomarkers and uncover the underlying the molecular mechanisms of WM progression using gene expression profiles from the Gene Expression Omnibus database. DEGs were identified using the LIMMA package and their potential functions were then analyzed by using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and the protein-protein interaction (PPI) network analysis by using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Data showed that among 1,756 DEGs, 926 were upregulated and 830 were downregulated by comparing WM BM CD19+ with normal PB CD19+ B cell samples, whereas 241 DEGs (95 upregulated and 146 downregulated) were identified by comparing WM BM CD138+ with normal BM CD138+ plasma cell samples. The DEGs were enriched in different GO terms and pathways, including the apoptotic process, cell cycle arrest, immune response, cell adhesion, mitogen-activated protein kinase signaling pathway, toll-like receptor signaling pathway, and the gonadotropin-releasing hormone signaling pathway. Hub nodes in the PPI network included CDK1, JUN, CREBBP, EP300, CAD, CDK2, and MAPK14. Bioinformatics analysis of the GSE9656 dataset identified 7 hub genes that might play an important role in WM development and progression. Some of the candidate genes and pathways may serve as promising therapeutic targets for WM.


Leukemia ◽  
2018 ◽  
Vol 32 (10) ◽  
pp. 2117-2125 ◽  
Author(s):  
Rebeqa Gunnarsson ◽  
Sebastian Dilorenzo ◽  
Kristina B Lundin-Ström ◽  
Linda Olsson ◽  
Andrea Biloglav ◽  
...  

2012 ◽  
Vol 11 ◽  
pp. CIN.S9542 ◽  
Author(s):  
Niklaus Fankhauser ◽  
Igor Cima ◽  
Peter Wild ◽  
Wilhelm Krek

Mutations in cancer-causing genes induce changes in gene expression programs critical for malignant cell transformation. Publicly available gene expression profiles produced by modulating the expression of distinct cancer genes may therefore represent a rich resource for the identification of gene signatures common to seemingly unrelated cancer genes. We combined automatic retrieval with manual validation to obtain a data set of high-quality gene microarray profiles. This data set was used to create logical models of the signaling events underlying the observed expression changes produced by various cancer genes and allowed to uncover unknown and verifiable interactions. Data clustering revealed novel sets of gene expression profiles commonly regulated by distinct cancer genes. Our method allows retrieval of significant new information and testable hypotheses from a pool of deposited cancer gene expression experiments that are otherwise not apparent or appear insignificant from single measurements. The complete results are available through a web-application at http://biodata.ethz.ch/cgi-bin/geologic .


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