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Molecular profiling of classical Hodgkin’s lymphoma tissues

ABSTRACT: Previous reports suggest that outcome of cHL patients may be related to the tumor microenvironment, which in turn may be influenced by EBV infection. Gene profiling was used for further characterize the cHL microenvironment. A training set of 73 cHL tissue samples was profiled using Affymetrix DNA microarrays. Supervised analysis provided a gene signature separating EBV+ from EBV- cHL tissues, including genes characteristic of Th1 and antiviral response. Samples from patients with favourable outcome significantly overexpressed genes involved in the function of B-cells and plasmacytoid dendritic cells (pDCs), like BCL11A. A validation set of 146 cHL samples was analyzed using immunohistochemistry (IHC). Keywords: Disease state analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE13996 | GEO | 2008/12/17

SECONDARY ACCESSION(S): PRJNA112495

REPOSITORIES: GEO

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Transcription profiling of human classical Hodgkinas lymphoma tissues

Project description:Previous reports suggest that outcome of cHL patients may be related to the tumor microenvironment, which in turn may be influenced by EBV infection. Gene profiling was used for further characterize the cHL microenvironment. A training set of 73 cHL tissue samples was profiled using Affymetrix DNA microarrays. Supervised analysis provided a gene signature separating EBV+ from EBV- cHL tissues, including genes characteristic of Th1 and antiviral response. Samples from patients with favourable outcome significantly overexpressed genes involved in the function of B-cells and plasmacytoid dendritic cells (pDCs), like BCL11A. A validation set of 146 cHL samples was analyzed using immunohistochemistry (IHC). Experiment Overall Design: A training set of 73 pre-treatment cHL tissue samples was profiled using Affymetrix DNA microarrays. They were collected at the time of diagnosis from 73 different cHL patients (including 10 children under the age of 15), who underwent lymph node surgical biopsy in several French haematological centres (Marseilles, Lille, Dijon, Nancy, Paris) belonging to the network of the Groupe d’Etude des Lymphomas de l’Adulte (GELA). Each patient (or parents for children) gave written informed consent. Samples were snap-frozen in liquid nitrogen within 30 minutes of removal. All cases were de novo reviewed by 2 hematopathologists (BC and LX) before analysis.

2009-01-06 | E-GEOD-13996 | biostudies-arrayexpress

Classical Hodgkin’s Lymphoma: Molecular evidence for specific alterations of circulating T lymphocytes

Project description:Gene expression profiles were performed from CD3+ T cells isolated from peripheral blood samples of untreated patients with cHL versus 2 control groups consisting of healthy donors and patients with sarcoidosis. Keywords = Hodgkin’s Lymphoma Keywords = T cell Keywords = immune regulation Keywords: repeat sample

2005-07-13 | GSE2657 | GEO

CGH profiling of 87 indolent non-hodgkin’s lymphoma (NHL)

Project description:BACKGROUND AND OBJECTIVES: Low-grade B-cell lymphomas include several subtypes of tumors with different degrees of histological, biological or clinical features. Differential diagnosis is frequently compromised by the lack of specific cytogenetic or molecular features. As a consequence, therapies remain in many lymphoma types largely based in common protocols with largely variable success. Our objectives were to describe and to compare the genomic profile of a series of samples from the most prevalent low-grade lymphoma subtypes; all of them systematically analyzed with the same approach. DESIGN-AND-METHODS: We carried out a high-resolution genomic DNA analysis (44K probes) in 87 low grade B cell lymphoma tumor samples that unambiguously presented the clinical picture, analytical features, and peripheral blood morphology and phenotype described for each entity. RESULTS: The genomic integrity of the samples was heavily compromised (80% of the tumors presented at least one aberration). This phenomenon also involved lymphoplasmocytic and marginal zone lymphomas that have not been previously studied by this genomic approach. New aberrations have been described for almost every subtype. We have also generated reports of the extension of the genomic instability, detecting distinct patterns of genomic instability within subtypes. INTERPRETATION-AND-CONCLUSIONS: The genomic profile of each subgroup showed substantive differences. The bioinformatic analysis of the data detected a set of new aberrations which were present in the majority of the subgroups and that pointed out to specific pathways, such as NF-kB (gains that involved REL, BCL11A and COMMD1) or DNA repair checkpoint pathways (deletion of 16q24 involving CDT1). Keywords: Comparative Genomic Hybridization - array; Genomic Instability

2008-01-01 | GSE8918 | GEO

Expression study of the Hodgkin’s lymphoma cell line L-1236 upon CRISPR Cas9-mediated knockout of lymphotoxin alpha (LTA) compared to control

Project description:Persistent NF-κB activation is a hallmark of the malignant Hodgkin/Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL). Analysis of the cHL cell-secreted key factors for NF-κB activation by chromatography and subsequent mass spectrometry revealed lymphotoxin-α (LTA) as the causative factor for autocrine and paracrine activation of canonical and noncanonical NF-κB in cHL cell lines. Upon CRISPR/Cas9-mediated gene knockout of LTA in the cell line L-1236, we performed expression analysis of LTA knockout versus control cells by using the Affymetrix array, Clariom S human, profiling tool.

2019-05-22 | GSE131559 | GEO

BCL11A: A Novel Breast Cancer Gene which Plays a Critical Role in Mammary Stem Cells and Progenitors

Project description:Triple negative breast cancer (TNBC) has poor prognostic outcome compared to other types of breast cancer1. At present the molecular and cellular mechanisms underlying TNBC pathology are not well understood1. Here we report that the transcription factor BCL11A is overexpressed in TNBC including basal-like breast cancer (BLBC) and that its genomic locus is amplified in up to 38% of BLBC tumours. BCL11A overexpression in immortalised human breast epithelial cells promotes tumour formation in xenograft models, whereas knockdown of BCL11A in TNBC cell lines suppresses their tumourigenic potential. In the DMBA-induced mouse mammary tumour model, Bcl11a is found to be essential for tumourigenesis since deletion of Bcl11a before DMBA treatment substantially decreases tumour formation, even in p53-null cells, and inactivation of Bcl11a in established tumours causes their regression. At the cellular level, BCL11A overexpression enhances clonogenicity in vitro whereas its deletion in the mouse causes a reduction in the number of mammary epithelial stem and progenitor cells. Thus, BCL11A has an important role in the genesis of TNBC and in normal mammary epithelial cells. This study highlights the importance of further investigation of BCL11A in breast cancer diagnosis and targeted therapies. [Mouse] KO is bcl11a deleted mammary stem cells. WT are mammary stem cells with intact Bcl11a. [Human] HMLE tumors overexpressing BCL11A.

2014-11-18 | E-GEOD-63386 | biostudies-arrayexpress

Expression study of the Hodgkin’s lymphoma cell line L-1236 upon CRISPR Cas9-mediated knockout of lymphotoxin alpha (LTA) compared to control

Project description:Persistent activation of canonical and non-canonical NF-κB pathways is a hallmark of the malignant Hodgkin and Reed-Sternberg cells in classical Hodgkin lymphoma (cHL). We identified lymphotoxin alpha (LTA), which is secreted by the cHL cell line L-1236 in high concentrations. This cytokine contributes to the constitutive activation of the canonical and non-canonical NF-κB pathways. L-1236 cells were purchased from the DSMZ (Braunschweig, Germany) and cultured in RPMI (Gibco) with 10% heat-inactivated fetal calf serum (FCS; Gibco). Cells were transducted with the lentiCRIPSPR v2 vector containing gRNAs which target the second (g2) and the fourth exon (g3) of LTA. Following single cell clonal selection, L-1236 control cells (v2) and two LTA knockout (KO) clones g2_1 and g3_4 were cultured in normal culture medium for 72 h. The RNA was extracted using the RNeasy kit (Qiagen) according to manufacturer’s instructions. Preparation of cDNA, fragmentation and labeling was performed with the GeneChIPTM WT PLUS reagent kit (ThermoFisher Scientific). Samples were hybridized to the human Clariom™ S Assay (ThermoFisher Scientific).

2019-01-24 | E-MTAB-6896 | biostudies-arrayexpress

Complex immune evasion strategies in classical Hodgkin lymphoma

Project description:The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T (Treg) cells and cytotoxic T cells. Th and Treg cells presumably provide essential survival signals for HRS cells. Treg cells are also involved in rescuing HRS cells from anti-tumor immune responses. An understanding of the immune evasion strategies of HRS cells is not only highly relevant for a characterization of the pathophysiology of cHL, but also clinically, given the current treatment approaches targeting checkpoint inhibitors. Here, we characterized the cHL-specific CD4+ T cell infiltrate regarding its role in immune evasion. Global gene expression analysis of CD4+ Th and Treg cells isolated from cHL lymph nodes and reactive tonsils revealed that Treg cell signatures were enriched in CD4+ Th cells of cHL. Hence, HRS cells may induce a Treg differentiation in Th cells, which was supported by in vitro studies with Th cells and cHL cell lines. Furthermore, we found indication for immune-suppressive purinergic signaling and a role of the inhibitory receptor-ligand pairs BTLA-HVEM and CD200R-CD200 in promoting immune evasion. Taken together, this study reveals that the immune evasion strategies in cHL are even more complex and multifaceted than previously recognized.

2017-10-09 | GSE102693 | GEO

Transcription profiling and idenrification of gene expression signatures associated with favourable or unfavourable treatment response and clinical outcome of Hodgkin lymphoma patients

Project description:Identification of gene expression signatures associated with favourable or unfavourable treatment response and clinical outcome of Hodgkin lymphoma patients.

2006-06-01 | E-MEXP-507 | biostudies-arrayexpress

Single-cell RNA-seq data of the tumor microenvironment of lymphocyte-rich Hodgkin lymphoma and other Hodgkin lymphoma subtypes

Project description:Lymphocyte-rich classic Hodgkin lymphoma (LR-CHL) is a rare subtype of Hodgkin lymphoma. Recent technical advances have allowed for the characterization of specific crosstalk mechanisms between malignant Hodgkin Reed-Sternberg (HRS) cells and different normal immune cells in the tumor microenvironment (TME) of CHL. However, the TME of LR-CHL has not yet been characterized at single cell resolution. Here, using single cell RNA sequencing, we examined the immune cell profile of 8 cell suspension samples of LR-CHL in comparison to 20 samples of the mixed cellularity (9 cases) and nodular sclerosis (11 cases) subtypes of CHL, as well as 5 reactive lymph node controls.

| EGAS00001005541 | EGA

Transcription profiling of the human K562 cell line treated with the polyamide-Chl conjugate 1R-Chl

Project description:To determine whether the polyamide-Chl conjugate 1R-Chl would cause similar changes in global gene expression in K562 cells, affymetrix gene chip analysis was performed using 1R-Chl. Through class comparison analysis, 1R-Chl affected the levels of transcription and genes of interest were determined. Experiment Overall Design: K562 cells were incubated with 1R-Chl (at 250 nM) or in the absence of polyamide, in triplicate for 24 h before RNA purification and microarray analysis at The Scripps Research Institute microarray facility. Affymetrix U133A Plus 2.0 GeneChips were hybridized in groups of three for each of the two groups. The Affymetrix probe set data were imported into BRB Arraytools (3.5.0 Beta 2), selecting the U133 chips used in the experiment and leaving all filters off.

2008-06-16 | E-GEOD-8832 | biostudies-arrayexpress

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