Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA121011 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Diffuse large B cell lymphoma is a heterogenous malignancy that is diagnosed in over 60,000 patients each year. Interleukin-21 has been shown to induce apoptosis in certain B cells originating from mice. Diffuse large B cell lyphomas express the Interleukin-21 Receptor yet the effects of Interleukin-21 on this malignancy are uknown. Identified genes responsive to IL-21 treatment in diffuse large B cell lymphoma.
2010-01-01 | GSE18967 | GEO
Project description:Abstract. Deregulated c-MYC is found in a variety of cancers where it promotes proliferation as well as apoptosis. In many hematological malignancies enhanced NF-kB exerts prosurvival functions. Here we investigated the role of NF-kB in mouse and human c-MYC-transformed lymphomas. The NF-kB-pathway is extinguished in murine lymphoma cells and extrinsic stimuli typically inducing NF-kB activity fail to activate this pathway. Genetic activation of the NF-kB pathway induces apoptosis in these cells, while inhibition of NF-kB by an IkBa superrepressor provides a selective advantage in vivo. Furthermore, in human Burkitt´s lymphoma cells we find that NF-kB activation induces apoptosis. NF-kB upregulates Fas and predisposes to Fas-induced cell death, which is caspase 8 mediated and can be prevented by CFLAR overexpression. We conclude that c-MYC overexpression sensitizes cells to NF-kB-induced apoptosis and persistent inacvtivity of NF-kB signaling is a prerequisite for MYC-mediated tumorigenesis. We could also show that low immunogenicity and Fas insensitivity of MYC driven lymphoma cells is reversed by activation of NF-kB. Our observations provide a molecular explanation for the described absence of the NF-kB signaling in Burkitt´s lymphoma and question the applicability of NF-kB inhibitors as candidates for treatment of this cancer.
2009-07-22 | GSE17129 | GEO
Project description:Lymphomagenesis in the presence of deregulated MYC expression requires suppression of MYC-driven apoptosis, often through downregulation of the pro-apoptotic BCL2L11 gene (Bim). Transcription factors (EBNAs) encoded by the lymphoma-associated Epstein-Barr virus (EBV) activate MYC and silence BCL2L11. We show that EBNA2 upregulates MYC by reconfiguring the 3 Mb MYC locus to increase upstream and decrease downstream enhancer-promoter interactions. EBNA2 recruits the SWI/SNF ATPase BRG1 to drive MYC enhancer-promoter interactions. MYC-Immunoglobulin translocation breakpoints in EBV-positive endemic Burkitt lymphoma localise to EBNA2-activated upstream MYC regions. This implicates EBV in the genesis and localisation of breakpoints, since active enhancers are targeted by activation-induced cytidine deaminase. We identify a novel haematopoietic BCL2L11 enhancer hub that is inactivated by EBNA3A and EBNA3C through recruitment of the H3K27 methyltransferase EZH2. Reversal of enhancer inactivation using an EZH2 inhibitor upregulates BCL2L11 and induces apoptosis. EBV therefore drives lymphomagenesis by hijacking long-range enhancer hubs and specific cellular co-factors. A study of MYC enhancer-promoter interactions using 4C on induction of MYC by Epstein-Barr virus infection of CD19+ primary B cells. B cells physiologically activated by treatment with CD40 ligand and IL-4 were studied as a control.
2016-08-04 | E-GEOD-82148 | biostudies-arrayexpress
Project description:MYC translocations are the biologic hallmark of Burkitt lymphomas but also occur in other mature B-cell lymphomas. If accompanied by chromosomal breaks targeting the BCL2 and/or BCL6 oncogenes, these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas (DHLs); otherwise, the term single-hit lymphoma (SHL) is applied. In order to characterize the biologic features of these MYC+ lymphomas other than Burkitt lymphomas, we explored, after exclusion of molecular Burkitt lymphoma (mBL) as defined by gene expression profiling (GEP), the molecular, pathological and clinical aspects of 80 MYC translocation (MYC+) lymphomas (31 SHL, 26 BCL2+/MYC+, 14 BCL6+/MYC+, 6 BCL2+/BCL6+/MYC+ and 3 MYC+ lymphomas with unknown BCL6 status). Comparison of SHL and DHL revealed no difference in frequency of MYC partner (IG/non-IG), genomic complexity or MYC expression and no differences in GEP. DHL showed a more frequent GCB-like GEP and higher IGH and MYC mutation rates. GEP revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ DHL. BCL2+/MYC+ DHL showed a more frequent GCB-like GEP. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In contrast to mBL and lymphomas without MYC break, SHL and DHL patients had similar poor outcome. Our data suggest that after excluding mBL, MYC+ lymphomas could be biologically widely lumped without further need for subclassification. 32 diffuse large B-cell lymphoma samples were hybridized to HG-U133A Affymetrix GeneChips. In addition, this study contains 30 already published samples, which contribute to GSE4475 (Hummel et al. 2006 (PMID 16760442)), as well as 18 already published samples from GSE22470 (Salaverria et al. 2011 (PMID 21487109)). No re-normalisation of the published samples was performed. The complete dataset representing: (1) the 32 diffuse large B-cell lymphoma Samples, (2) the 30 Samples from GSE4475 and (3) the 18 Samples from GSE22470, is linked below as a supplementary file
2013-12-31 | E-GEOD-44164 | biostudies-arrayexpress
Project description:<p>Cutaneous diffuse large B cell lymphomas (DLBCL) are aggressive lymphomas with a poor prognosis. To elucidate their genetic bases, we performed whole exome capture and massively parallel sequencing on 19 tumor samples of diffuse large B cell lymphoma, leg type (DLBCL-LT) and 6 samples of secondary cutaneous diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS). Tumor specimens and their associated sequencing data were from multiple institutions, including Northwestern University (Chicago, IL), Massachusetts General Hospital (Boston, MA), and Medical University of Graz (Graz, Austria).</p>
| phs001645 | dbGaP
Project description:The distinction between the Burkitt lymphoma and diffuse large B-cell lymphoma is imprecise using current diagnostic criteria. We applied transcriptional and genomic profiling to molecularly define Burkitt lymphoma. Gene expression profiling employing Affymetrix GeneChips (U133A) was performed in 220 mature aggressive B-cell lymphomas, including a core group of eight Burkitt lymphomas, which fulfilled all diagnostic criteria of the WHO classification. A molecular signature of Burkitt lymphoma was generated. Chromosomal abnormalities were detected by interphase fluorescence in-situ hybridization and array comparative genomic hybridization. The molecular Burkitt lymphoma signature identified 44 cases. Fifteen of these cases lacked a morphology typical for Burkitt/Burkitt-like lymphoma. The vast majority (88%) of the 176 lymphomas without the molecular Burkitt lymphoma signature represented diffuse large B-cell lymphomas. In 20% of these cases a MYC break was detectable which was associated with complex chromosomal changes. Our molecular definition of Burkitt lymphoma sharpens and extends the spectrum of Burkitt lymphoma. In mature aggressive B-cell lymphomas without a Burkitt lymphoma signature, a chromosomal break in the MYC locus proved to be associated with adverse clinical outcome. Experiment Overall Design: 220 diffuse large B-cell lymphoma and Burkitt lymphoma samples hybridized to 221 HGU133A Affymetrix GeneChips
2008-06-13 | E-GEOD-4475 | biostudies-arrayexpress
Project description:In this model, TLR2-TLR6 mediates MyD88 pathway gets activated, which activates IL-12 production and induces iNOS expression when the Macrophage is infected with Leishmania parasite. The early induction of IL-10 takes place which leads to the induction of NFIL3, HDAC3, and SHP-1. They inhibit IL-12 production and thus hamper IL-12 induced IFN-gamma mediated; Nitric oxide production. A key transcription factor NFAT5 connects IL-12 and IL-10 pathways. It upregulates IL-12 and downregulates IL-10. In this model, NFAT5 is downregulated which is also inhibiting IL-12.
2022-01-24 | MODEL2012040002 | BioModels
Project description:Lymphomagenesis in the presence of deregulated MYC expression requires suppression of MYC-driven apoptosis, often through downregulation of the pro-apoptotic BCL2L11 gene (Bim). Transcription factors (EBNAs) encoded by the lymphoma-associated Epstein-Barr virus (EBV) activate MYC and silence BCL2L11. We show that EBNA2 upregulates MYC by reconfiguring the 3 Mb MYC locus to increase upstream and decrease downstream enhancer-promoter interactions. EBNA2 recruits the SWI/SNF ATPase BRG1 to drive MYC enhancer-promoter interactions. MYC-Immunoglobulin translocation breakpoints in EBV-positive endemic Burkitt lymphoma localise to EBNA2-activated upstream MYC regions. This implicates EBV in the genesis and localisation of breakpoints, since active enhancers are targeted by activation-induced cytidine deaminase. We identify a novel haematopoietic BCL2L11 enhancer hub that is inactivated by EBNA3A and EBNA3C through recruitment of the H3K27 methyltransferase EZH2. Reversal of enhancer inactivation using an EZH2 inhibitor upregulates BCL2L11 and induces apoptosis. EBV therefore drives lymphomagenesis by hijacking long-range enhancer hubs and specific cellular co-factors. A study of MYC enhancer-promoter interactions using 4C on induction of MYC by the Epstein-Barr virus transcription factor EBNA2 in a lymphoblastoid cell line.
2016-08-04 | E-GEOD-82149 | biostudies-arrayexpress
Project description:Plasmablastic lymphoma is a high grade B cell lymphoma with plasmablastic morphology and a terminally differentiated B cell immunophenotype, usually arising in the setting of immunodeficiency and often demonstrating Epstein Barr Virus positivity. The molecular and genetic mechanisms underlying the pathogenesis of PBL are largely unknown. To better understand its pathogenesis, herein we have analyzed global gene expression of PBL and compared that to gene expression profiles of diffuse large B cell lymphoma. While overlaps in transcriptomes between these malignancies were identified, we have shown that the gene expression profile of plasmablastic lymphoma is distinct, demonstrating striking downregulation of B cell receptor signaling genes, BCL6, BCL11A SPI-B, targets of NFKB1, and upregulation of mitochondrial genes, PRMT5, MYC and MYC targets and IL21, implicating these alterations in the pathogenesis of this lymphoma. In addition we show the usefulness of SWAP-70 immunohistochemistry in the differentiation of immunoblastic diffuse large B cell lymphoma and plasmablastic lymphoma. Our findings provide justification for considering plasmablastic lymphoma as a specific lymphoma entity and provide insight into the unique transcriptional aberrations occurring in this high-grade lymphoma. Expression profiles of 15 plasmablastic lymphomas and 10 diffuse large B-cell lymphomas were obtained using Afymmetrix U133A2 microarrays.
2015-09-15 | E-GEOD-53117 | biostudies-arrayexpress