Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA319490 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Multiple types of B-cell lymphoma respond clinically to BTK inhibition, reflecting their dependence on B-cell receptor signaling. The germinal center B-cell subtype of diffuse large B-cell lymphoma resists BTK inhibition, but we found that B-cell receptor elimination in cell lines of this lymphoma type reduced their size and proliferation. Their B-cell receptor signals in a “tonic”, antigen-independent manner, requiring SYK, CD19, and phosphorylation of a specific tyrosine residue in the CD79A immunoreceptor tyrosine-based activation motif domain. The effect of B-cell receptor elimination or inhibition in these lines is proportional to their B-cell receptor surface density and its relative contribution to AKT activity, on which these lines uniformly depend, and is rescued by spontaneous or induced loss of PTEN protein. Biomarker-guided targeting of tonic B-cell receptor signaling may improve treatment of germinal center B-cell lymphoma.
2017-01-01 | GSE80615 | GEO
Project description:B-cell receptor (BCR) signaling promotes the survival of malignant B cells, such as Burkitt’s lymphoma (BL) and the activated B-cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). In contrast to ABC DLBCL, where malignant cells require chronic activation of the BCR for their survival, BL cells are dependent on tonic BCR signaling that is antigen-independent. Elucidation and systematic comparison of tonic and activated BCR signaling led to the identification of novel signaling effectors, among them ACTN4 and ARFGEF2, which were identified as regulators of BL cell survival. As tonic and activated BCR signaling are relevant for important aspects of B cell biology, our study helps in gaining an understanding of BCR-induced processes not only in malignant but potentially also physiological settings.
2016-05-09 | PXD003492 | Pride
Project description:Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, including two main molecular subtypes termed activated B cell-like (ABC) and germinal center B cell-like (GCB). ABC DLBCL is less curable and identification of new molecular targets is needed for the development of effective therapeutic agents. Here, we focused on EGR1, a transcription factor that is regulated by the B cell receptor and JAK1/STAT3 signaling pathway in ABC DLBCL. ChIP-Seq and RNA-Seq analyses revealed that gene regulation by EGR1 in ABC DLBCL accentuates multiple oncogenic pathways, including MYC and E2F, while dampening the lethal type I IFN pathway.
2021-08-06 | GSE123291 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) is currently divided into three main molecular subtypes, defined by gene expression profiling (GEP): Germinal Center B-cell like (GCB), Activated B-Cell like (ABC), and Primary Mediastinal B-cell Lymphoma (PMBL). DLBCL subtypes were determined according to patients' gene expression profiles.
2017-01-30 | GSE87371 | GEO
Project description:The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. METHODS: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. RESULTS: Three gene-expression subgroups--germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma--were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators.
2016-12-07 | GSE90953 | GEO
Project description:IRF8, a transcriptional factor, has the heightened expression in germinal center(GC) B cell and GC-origin B cell lymphoma. To identify IRF8 direct targets in GC B cells, ChIP-chip ananlysis was done in three different GC-origin diffuse large B cell lymphoma cell lines. IRF8-negative cell lines, MPC11, was also used as a negatvie control.
2011-10-15 | GSE30519 | GEO
Project description:IRF8, a transcriptional factor, has the heightened expression in germinal center(GC) B cell and GC-origin B cell lymphoma. To identify IRF8 direct targets in GC B cells, ChIP-chip ananlysis was done in three different GC-origin diffuse large B cell lymphoma cell lines. IRF8-negative cell lines, MMS1, was also used as a negatvie control.
2011-10-15 | GSE30357 | GEO
Project description:PU.1, a transcriptional factor, is expressed in wide range of B cells from early to mature stage. To identify PU.1 direct targets in germinal center B cells, ChIP-chip ananlysis was done in three different GC-origin diffuse large B cell lymphoma cell lines.
2011-10-15 | GSE30520 | GEO
Project description:Diffuse Large B-Cell Lymphoma (DLBCL) is the most common aggressive form of non-Hodgkin lymphoma with variable biology and clinical behavior. The current classification does not fully explain the biological and clinical heterogeneity of DLBCLs. In this study we carried out genome-wide DNA methylation profiling of 140 DLBCL samples and 10 normal germinal center B-cells (NGCBs) using the HELP assay and hybridization to a custom Roche NimbleGen promoter array. We defined methylation disruption as a main epigenetic event in DLBCLs and designed a method for measuring the methylation variability of individual cases. We then used a novel approach for unsupervised hierarchical clustering based on the extent of DNA methylation variability. This approach identified 6 clusters (A-F). The extent of methylation variability was associated with survival outcomes, with significant differences in overall and progression-free survival. The novel clusters are characterized by disruption of specific biological pathways like cytokine-mediated signaling, ephrin signaling and pathways associated with apoptosis and cell cycle regulation. In a subset of patients, we profiled gene expression and genomic variation to investigate their interplay with methylation changes. This study is the first to identify novel epigenetic clusters of DLBCLs and their aberrantly methylated genes, molecular associations and survival. DNA methylation profiling in 140 primary denovo Diffuse Large B cell Lymphoma (DLBCL) samples from patients that had undergone R-CHOP chemotherapy and 10 purified normal Germinal Center B Cells
2014-01-18 | E-GEOD-54200 | biostudies-arrayexpress
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumors. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumors of DLBCL patients, apparently reflecting the variation in tumor proliferation rate, host response and differentiation state of the tumor. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal center B cells ('germinal center B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal center B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumors on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. This study is described more fully in Alizadeh AA et al.(2000) Nature 403:503-11
2002-06-27 | E-GEOD-60 | biostudies-arrayexpress