Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA128883 | ENA |
REPOSITORIES: ENA
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Project description:The microarray analysis showed an interesting up-regulation in the set of genes controlling the development of Th1, mainly IFN-gamma, and other type 1 interferon response genes including CXCL10 in IRF4 knocked-down HuT-102 cells. HuT-102 cells, a human cutaneous T cell lymphoma, were transiently transfected with siRNAs against human IRF4 or firefly luciferase. Cells were incubated for 60 h at 37 centigrade. Total RNA samples were prepared from the cells. Gene expression was analyzed by an Affymetrix GeneChip® system with a Human Genome U133-plus 2.0 array for analysis of over 47,000 transcripts. Sample preparation for array hybridization was carried out as described in the manufacturerâs instructions.
2010-06-08 | E-GEOD-22036 | biostudies-arrayexpress
Project description:Identification of genes that are regulated by TAK1 in human cutaneous T cell lymphoma HuT-102 cells
| PRJNA117159 | ENA
Project description:We previously reported that human T cell lymphotropic virus 1 (HTLV-1) Tax oncoprotein constitutively activates TAK1. Here, we established Tax-positive HuT-102 cells stably downregulated TAK1 expression by short-hairpin RNA (HuT-shTAK1 cells), and investigated the physiological function of TAK1. Microarray analysis demonstrated that several interferon (IFN)-inducible genes including chemokines such as CXCL10 and CCL5 were significantly downregulated in HuT-shTAK1 cells. In contrast, Tax-mediated constitutive activation of NF-kB was intact in HuT-shTAK1 cells. IRF3, a critical transcription factor in innate immunity to viral infection, was constitutively activated in a Tax-dependent manner. Activation of IRF3 and IRF3-dependent gene expression were dependent on TAK1 and TBK1. On the other hand, IRF4, another IRF family of transcription factor overexpressed in a Tax-independent manner, negatively regulated the TAK1-dependent IRF3 transcriptional activity. Together, HTLV-1 manipulates IFN signaling by regulating both positive and negative IRFs. HuT-102 cells, a human cutaneous T cell lymphoma, were stably transfected with shRNA expression vectors against human MAP3K7 (TAK1) or firefly luciferase (Luc). The cells were maintained in media containing 0.5 mg/ml G418. For the experiment, the cells were incubated in media without G418 for 36 h at 37M-BM-0C. Total RNA samples were prepared from the cells. Gene expression was analyzed by an Affymetrix GeneChipM-BM-. system with a Human Genome U133-plus 2.0 array for analysis of over 47,000 transcripts. Sample preparation for array hybridization was carried out as described in the manufacturerM-bM-^@M-^Ys instructions. Two replicates per sample type.
2009-08-18 | E-GEOD-16219 | biostudies-arrayexpress
Project description:We report the characterization of a recurrent somatic mutation c.295T>C (p.C99R) in the Interferon Regulatory Factor 4 (IRF4) gene in human lymphoma in the α3-recognition helix of the IRF4 DNA-binding domain. IRF4-C99R fundamentally alters IRF4 DNA-binding, combining loss-of-binding at canonical IRF motifs and neomorph gain-of-binding at canonical and non-canonical IRF composite elements (CEs). IRF4-C99R thoroughly modifies IRF4 function, blocking IRF4-dependent plasma cell induction, and specifically up-regulating lymphoma-specific genes in a degenerate Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner.
2023-07-21 | E-MTAB-12522 | biostudies-arrayexpress
Project description:In 20% of IRF4 deficient mice older than 150 days, spontaneous highly malignant pre B cell lymphomas emerge. A change in the expression profile of genes involved in tumor progession and malignancy is sought for by microarray analyses. We used microarrays to detail the global programme of gene expression underlying tumor development and identified distinct classes of up-regulated and downregulated genes in the spontaneous highly malignant pre B cell lymphoma. Tumor mouse cells, control mouse B cells lacking IRF4 and control wildtype mouse B cells were purified for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the different expression levels of genes in tumor cells vs. control cells in order to find specific tumor regulated genes. To that end, we used cells from murine tumors, control mouse B cells lacking IRF4 from bone marrow and sorted accourding to CD19+, sIgM- (control mice IRF4 Knockout ), and control wildtype mouse B cells from bone marrow sorted accourding to CD19+, CD25+, sIgM- (control mice wildtype C57Bl6).
2015-05-01 | E-GEOD-67161 | biostudies-arrayexpress
Project description:Interferon regulatory factor 4 (IRF4) is a master transcription factor required for the maturation of germinal center B cells that eventually develop into antibody secreting plasma cells and memory B cells. IRF4-deficient mice exhibit a profound reduction in serum immunoglobulin levels. In spite of wealth of the information relating to IRF4 and B cell biology, little is known about the intricate molecular details of the role of this transcription factor during B cell development. We therefore examined the genome-wide targets of IRF4 by ChIP-chip analysis in GC derived BL2 Burkittâs lymphoma cells. ChIP studies were further supplemented by whole genome expression analysis after shRNA-mediated knockdown of IRF4. Our study revealed that IRF4 regulates expression of genes important for a) BCR signaling b) antigen processing and presentation by MHC. In addition we found that IRF4 possibly in some way involved to regulate LTA, LTB and CXCR5 those involved in immune system development, particularly light zone development related genes such as FDC clustering regulating and IL21R and IL10 who are involved in B cell development.. On the other hand, IRF4 suppressesd genes in the oxidative phosphorylation pathway. Our findings illuminate hitherto unexplored roles of IRF4 in GC B cell development. BL2 Burkitt's lymphoma-derived B cells were infected with lentivirus expressing shRNA for IRF4 or control, and total RNA was subjected to Illumina BeadsExpression Arrays analysis.
2015-12-15 | E-GEOD-64269 | biostudies-arrayexpress
Project description:RNA interference screens identified the transcription factor IRF4 as essential for the survival of the activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL). Analysis of IRF4 genomic targets in ABC-DLBCL and Multiple Myeloma (MM) revealed that IRF4 regulates distinct networks in these cancers. IRF4 peaks in ABC-DLBCL, but not MM, were enriched for a composite ETS-IRF DNA motif that can be bound by heterodimers of IRF4 and the ETS-family transcription factor SPIB, whose expression is also essential for ABC-DLBCL survival. Gene expression and ChIP-Seq analysis identified essential genes co-regulated by IRF4 and SPIB. Together, these factors regulate a critical oncogenic loop by activating CARD11, which controls ABC-DLBCL survival via the NF-kB pathway. The interaction between IRF4 and SPIB presents an attractive therapeutic target in this aggressive lymphoma.
2012-08-16 | GSE32456 | GEO
Project description:Background: Germinal center B-cell (GCB) lymphomas are common in children and adults. The prognosis strongly depends on age. Subgroups of GCB-lymphomas are characterized by chromosomal translocations affecting immunoglobulin (IG) loci leading to oncogene deregulation. Methods: Novel IG translocation partners were cloned within the network “Molecular Mechanisms in Malignant Lymphomas” (MMML) by long-distance inverse polymerase chain reaction. Mature aggressive B-cell lymphomas from the MMML as well as pediatric and adult lymphoma trials were analyzed by fluorescence in situ hybridization (FISH) and immunhistochemistry. Data from 438 MMML cases characterized by gene expression profiling were mined. Results: Cloning of unknown IG partners identified a t(6;14)(p25;q32) juxtaposing the IRF4 oncogene with the IGH-locus as novel recurrent aberration in GCB lymphoma. FISH analyses of 427 mature B-cell lymphomas for IRF4 translocations revealed 20 IG/IRF4 positive lymphomas (17 IGH/IRF4, 2 IGL/IRF4, 1 IGΚ/IRF4). IG/IRF4-positive lymphomas were predominantly GCB-type diffuse large B-cell lymphomas (DLBCL) or follicular lymphoma grade 3, shared overexpression of IRF4/MUM1 and BCL6 and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas was different from other subtypes of DLBCL and a classifier for IG/IRF4 positivity containing 27 genes allowed prediction of 3 additional MMML IG/IRF4-positive cases subsequently proven by FISH. IG/IRF4-positivity was associated with a favorable outcome likely due to significant enrichment of IG/IRF4-positive lymphomas in childhood and young adulthood. Conclusions: Our results suggest IRF4 translocations to be primary genetic alterations in a novel molecularly defined subset of GC-derived lymphomas predominantly affecting children. 271 diffuse large B-Cell lymphoma samples were hybridized to HGU133A Affymetrix GeneChips.
2011-06-24 | E-GEOD-22470 | biostudies-arrayexpress
Project description:We studied gene expression profiles of 17 cutaneous B-cell lymphomas that were collected with 4-6 millimeter skin punch biopsies. We also included tissue from 2 cases of mycosis fungoides (MF), 3 normal skin biopsies and 3 tonsils to create a framework for further interpretation. A hierarchical cluster algorithm was applied for data analysis. Our results indicate that small amounts of skin tissue can be used successfully to perform microarray analysis and result in distinct gene expression patterns. Duplicate specimens clustered together demonstrating a reproducible technique. Within the cutaneous B-cell lymphoma specimens two specific B-cell differentiation stage signatures of germinal center B-cells and plasma cells could be identified. Primary cutaneous follicular and primary cutaneous diffuse large B-cell lymphomas had a germinal center B-cell signature while a subset of marginal zone lymphomas demonstrated a plasma cell signature. Primary and secondary follicular B-cell lymphoma of the skin were closely related, despite previously reported genetic and phenotypic differences. In contrast primary and secondary cutaneous diffuse large B-cell lymphoma were less related to each other. This pilot study allows a first glance into the complex and unique microenvironment of B-cell lymphomas of the skin and provides a basis for future studies, that may lead to the identification of potential histologic and prognostic markers as well as therapeutic targets.
2005-10-07 | E-SMDB-1798 | biostudies-arrayexpress
Project description:Anaplastic large cell lymphoma (ALCL) is a main type of T cell lymphomas and comprises three distinct entities: systemic ALK+, systemic ALK- and cutaneous ALK- ALCL. Little is known about their pathogenesis and their cellular origin, and morphological and immunophenotypical overlap exists between ALK- ALCL and classical Hodgkin lymphoma (cHL). We conducted gene expression profiling of microdissected lymphoma cells of ALK+ and ALK- systemic ALCL, cutaneous ALCL and cHL, and of eight subsets of normal T and NK cells. The analysis supports a derivation of ALCL from activated T cells, but the lymphoma cells acquired a gene expression pattern hampering an assignment to a CD4+, CD8+ or CD30+ T cell origin. Indeed, ALCL display a general down-modulation of T cell characteristic molecules. All ALCL types show significant expression of NFκB target genes and upregulation of genes involved in oncogenesis (e.g. EZH2). Surprisingly few genes are differentially expressed between systemic and cutaneous ALK- ALCL despite their different clinical behaviour, and between ALK- ALCL and cHL despite their different cellular origin. ALK+ ALCL are characterized by expression of genes regulated by pathways constitutively activated by ALK. This study provides multiple novel insights into the molecular biology and pathogenesis of ALCL.
2009-11-16 | GSE14879 | GEO