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Expression data of diagnostic biopsy samples from Hodgkin lymphoma patients

ABSTRACT: Despite advances in Hodgkin lymphoma (HL) treatment, about 20% of patients still die due to progressive disease. Current prognostic models predict treatment outcome with imperfect accuracy, and clinically relevant biomarkers are yet to be established that improve upon the International Prognostic Scoring (IPS) system. We analyzed 130 frozen diagnostic lymph node biopsies from classical HL patients by gene expression profiling to describe cellular signatures correlated with treatment outcome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE17920 | GEO | 2010/03/01

SECONDARY ACCESSION(S): PRJNA120053

REPOSITORIES: GEO

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Expression data of diagnostic biopsy samples from Hodgkin lymphoma patients

Project description:Despite advances in Hodgkin lymphoma (HL) treatment, about 20% of patients still die due to progressive disease. Current prognostic models predict treatment outcome with imperfect accuracy, and clinically relevant biomarkers are yet to be established that improve upon the International Prognostic Scoring (IPS) system. We analyzed 130 frozen diagnostic lymph node biopsies from classical HL patients by gene expression profiling to describe cellular signatures correlated with treatment outcome. Diagnostic fresh-frozen lymph node specimens from 130 patients with cHL were selected for GEP from the tissue archive at the British Columbia Cancer Agency and the University of Nebraska Medical Center according to the following criteria: primary diagnosis of cHL following central review, representative lymph node tissue (at least 1 cmÂ² area in tissue sections), HIV-negative status and first line treatment with systemic chemotherapy ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or ABVD-like regimen with or without radiation therapy if indicated or, in the case of seven patients with limited-stage disease, wide field radiation.

2010-03-08 | E-GEOD-17920 | biostudies-arrayexpress

Transcription profiling of Hodgkin Lymphoma- and Anaplastic Large Cell Lymphoma-derived cell lines

Project description:To identify genes and pathways involved in the pathogenesis of Hodgkin Lymphoma (HL) and Anaplastic Large Cell Lymphoma (ALCL) , we used the Ontario Cancer Institute (OCI) Human 27k arrays (UNH Homo sapiens 19K8 array), to study the expression profiling in pairs of HL-derived cell lines (KMH2 and L428) and ALCL-derived cell lines (DEL and SR-786).

2009-03-31 | E-MEXP-1132 | biostudies-arrayexpress

Functional characteriation of histone variant H2A.B in Hodgkin lymphoma

Project description:The fact that the testis-specific H2A.B is ectopically expressed in Hodgkin lymphoma (HL) and its derived cell lines implicates H2A.B in having a role in oncogenesis (either as an oncogene or a tumour suppressor) similar to other epigenetic regulators of the testis. In order to understand the mechanism of H2A.B-mediated epigenetic regulation in Hodgkin lymphoa, the epigenomic profiles of pan-H2A.B and major H2A.B post-translational modificaitons were investigated using the CUT&RUN method.

2021-06-02 | GSE158239 | 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

Long non-coding RNA expression profiling in normal B-cell subsets and Hodgkin lymphoma reveals Hodgkin and Reed-Sternberg cell specific long non-coding RNAs

Project description:Hodgkin lymphoma (HL) is a malignancy of germinal center (GC) B-cell origin. To explore the role of long non-coding RNAs (lncRNAs) in HL, we studied lncRNA expression patterns in normal B-cell subsets, HL cell lines and tissues. Naive and memory B-cells showed a highly similar lncRNA expression pattern, distinct from GC-B cells. Significant differential expression between HL and normal GC-B cells was observed for 475 lncRNA loci. For two validated lncRNAs an enhanced expression was observed in HL, diffuse large B cell lymphoma and lymphoblastoid cell lines. For a third lncRNA, increased expression levels were observed in HL and part of Burkitt lymphoma cell lines. RNA-FISH on primary HL tissues revealed a tumor cell-specific expression pattern for all three lncRNAs. A potential cis-regulatory role was observed for 107 differentially expressed lncRNA-mRNA pairs localizing within a 60kb region. In line with a cis-acting role, we showed a preferential nuclear localization for two selected candidates. Thus, we showed dynamic lncRNA expression changes during the transit of normal B-cells through the GC reaction and widely deregulated lncRNA expression patterns in HL. Three lncRNAs showed a tumor cell-specific expression pattern in HL tissues and might therefore be of value as a biomarker.

2016-05-26 | GSE81086 | GEO

Downregulation of STAT3 in EBV-positive Hodgkin lymphoma

Project description:STAT3 encodes an oncogenic transcription factor which is activated via various signalling pathways or Epstein Barr virus (EBV)-infection. The tumor cells of Hodgkin lymphoma (HL) are derived from germinal center B-cells and transformed by chromosomal rearrangements, aberrant signal transduction, downregulation of transcription factors mediating B-cell differentiation, and EBV-infection. HL cell lines represent useful models to investigate the molecular pathology and deduced treatment options in this malignancy. Using cell line L-540, we have recently shown that constitutively activated STAT3 drives aberrant expression of hematopoietic NKL homeobox gene HLX. Here, we analyzed HL cell line AM-HLH which is EBV-positive but nevertheless HLX negative. Consistently, AM-HLH expressed decreased levels of STAT3 proteins which were additionally inactivated and located in the cytoplasm. Combined genomic and gene expression profiling data revealed amplified and overexpressed candidates involved in opposed regulation of STAT3 and EBV. Subsequent analyses demonstrated that IRF4 and NFATC inhibited STAT3 expression. However, treatment with IL6 or IL27 activated STAT3, elevated expression of HLX and MIR155, and inhibited IRF4. MIR155 (STAT3 target gene) and BCL11A and SPIB (target genes of HLX) are described as suppressors and activators of EBV and showed reduced and elevated expression levels in AM-HLH, respectively. Taken together, this cell line deals with two conflicting oncogenic drivers, namely JAK2-STAT3-signalling and EBV-infection but is sensitive to cytokine signalling, mediating a switch between these aberrant pathways. Thus, AM-HLH represents an interesting cell line model to study the pathogenic roles of STAT3 and EBV and their therapeutic implications in HL.

2022-12-31 | GSE204717 | GEO

Effects of the novel PI3K δ/γ inhibitor RP6530 on global gene expression in Hodgkin Lymphoma cell lines.

Project description:Tumor-associated macrophages (TAMs) are involved in the pathogenesis of Hodgkin lymphoma (HL) and correlate with negative prognosis. The phosphatidylinositol 3-kinase (PI3K) mediates tumor and endothelial cell survival, and macrophage activation. As PI3Kδ and PI3Kγ are constitutively activated in HL, we describe RP6530, a novel PI3Kδ/γ inhibitor, in clinical development for HL and NHL. RP6530 exhibits anti-proliferative and cytotoxic activity both in vitro in HL cell lines and in vivo in HL xenograft mouse models. By inhibiting the metabolic regulator Pyruvate Kinase M2 (PKM2), RP6530 downregulates lactic acid metabolism in HL cells switching the activation of macrophages from an immunosuppressive M2-like phenotype to a more inflammatory M1-like state. RP6530 reshapes the tumor microenvironment (TME), through the re-polarization of TAMs into pro-inflammatory macrophages and the inhibition of tumor vasculature. These data demonstrate the central role of PI3K δ/γ inhibition for targeting HL cells and TME, indicating RP6530 as a novel therapeutic opportunity for HL patients.

2020-09-07 | GSE105439 | GEO

Expression data from Hodgkin lymphoma cell lines UHO-1 and L-1236 transduced with shRNAs against GATA-3 or non-functional control shRNAs

Project description:The transcription factor network in Hodgkin lymphoma (HL) represents a unique composition of proteins found in no other hematopoietic cell. Among these factors, an aberrant expression of the T cell transcription factor GATA-3 is observed in the B cell-derived Hodgkin and Reed/Sternberg (HRS) tumor cells. Herein, we elucidated the regulation and function of this factor in HL To obtain a more comprehensive overview of GATA-3 regulated genes in cHL cell lines, we performed a gene chip analysis comparing gene expression in GATA-3-specific shRNA-transduced L-1236 and U-HO1 cells compared to samples transduced with vectors encoding scrambled shRNAs.

2010-07-24 | GSE22550 | GEO

MicroRNA-24-3p is overexpressed in Hodgkin lymphoma and protects Hodgkin and Reed-Sternberg cells from apoptosis [ChIP-chip]

Project description:Micro (mi)RNAs not only play important roles in biological processes such as proliferation, metabolism, differentiation and apoptosis, but also in diseases such as cancers. We identified miRNAs with deregulated expression in Hodgkin lymphoma (HL) and investigated their role in the pathogenesis of HL. Small RNA sequencing revealed 84 significantly differentially expressed miRNAs in HL cell lines as compared to GC-B cells. Three upregulated miRNAs, miR-23a-3p, miR-24-3p and miR-27a-3p, were derived from one primary-miRNA transcript. Loss-of-function analysis for these miRNAs and their seed family members resulted in decreased growth upon miR-24-3p inhibition in three and of miR-27a/b-3p inhibition in one HL cell line. Apoptosis analysis indicated that the effect of miR-24-3p on cell growth is at least in part caused by an increase of apoptotic cells. Argonaute 2 (Ago2)-IP revealed 1,142 genes consistently targeted by miRNAs in at least three out of four HL cell lines. Furthermore, 52 out of the 1,142 genes were predicated targets of miR-24-3p. Functional annotation analysis revealed a function related to cell growth, cell death and/or apoptosis for 15 out of the 52 genes. Western blotting of the top-5 genes showed increased protein levels upon miR-24-3p inhibition for CDKN1B and MYC. In summary, we showed that miR-24-3p is upregulated in HL and its inhibition impaired cell growth possibly via targeting CDKN1B and MYC.

2017-02-26 | GSE92615 | GEO

Expression data from Hodgkin lymphoma cell lines L-428 and L-1236: L-428 and L-1236 cells were transduced with tGFP-EBF1 or as control tGFP-only.

Project description:The transcription factor network in Hodgkin lymphoma (HL) represents a unique composition of proteins found in no other hematopoietic cell. An aberrant downregulation of the B cell transcription factor EBF1 is observed in the B cell-derived Hodgkin and Reed/Sternberg (HRS) tumor cells. Herein, we elucidated the consequences of the down regulation of this factor in HL. To obtain a more comprehensive overview of EBF1 regulated genes in cHL cell lines, we performed a gene chip analysis comparing gene expression in tGFP-EBF1-transduced L-1236 and L-428 cells compared to samples transduced with vectors encoding only tGFP.

2012-11-01 | GSE41493 | GEO

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