Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells From Brentuximab-Vedotin Induced Injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA642881 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To determine differential expression of miRNA in classical Hodgkin lymphoma diseased nodes compared to non-malignant lymph nodes, we used agilent microarray release 16 and quantile normalisation using Genespring GX software to quantify and compare miRNA expression.. Total RNA was extracted from 8 non-malignant lymph node and 14 classical Hodgkin lymphoma diseased node (6 mixed cellularity and 8 nodular sclerosing) formalin-fixed paraffin-embedded tissue samples
2013-03-19 | E-GEOD-45264 | biostudies-arrayexpress
Project description:Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts (CAF). However, to date a deep molecular characterization of these fibroblasts is lacking. Aim of the present study therefore was a comprehensive characterization of these fibroblasts.
2020-06-30 | GSE153517 | GEO
Project description:Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (MYOCD) expression. Moreover, TIMP3, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL.
| S-EPMC6896072 | biostudies-literature
Project description:Classical Hodgkin lymphoma (cHL) is a highly curable disease, with about 80% of patients cured using standard first-line chemotherapy. However, outcomes for relapsed/refractory patients re-main unfavorable and there is a critical lack of predictive biomarkers for early identification of these patients who may benefit from new therapeutic strategies. Here we evaluated the dynamic expression of 571 immune-related genes in a cohort of 42 cHL using NanoString technology. We identified a 19-genes immune signature predictive of relapse at the time of diagnosis, which was found to be strongly dependent on histological subtype. Moreover, comparative analyses be-tween paired diagnostic/relapsed biopsies of nodular sclerosis cHL showed 134 differentially expressed genes, highlighting an immune contexture shift at relapse not found in the mixed-cellularity subtype. Overall, these results strongly suggest that the predictive value of immune signature in cHL is influenced by histological subtype, a criterion that should be con-sidered when assessing new immunotherapy strategies.
2022-10-10 | GSE212902 | GEO
Project description:Hodgkin lymphoma is derived from germinal center / post-germinal center B cells. To determine differentially expressed genes between Hodgkin Reed Sternberg cells and their presumed cell of origin we investigated the expression profiles of 5 commonly used Hodgkin lymphoma cell lines as compared to reactive germinal centers.
2010-12-11 | E-GEOD-25986 | biostudies-arrayexpress
Project description:Analysis of differential gene expression in human non-Hodgkin`s lymphoma cell lines and a primary leukaemic tumor sample of large cell anaplastic type in comparison with Hodgkin`s lymphoma cell lines and other non-Hodgkin`s lymphoma samples and non-neoplastic lymphocytes Experiment Overall Design: Samples were analyzed to be compared to publically available data sets
2008-06-13 | E-GEOD-4109 | biostudies-arrayexpress
Project description:The pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly due to the technical challenge of analyzing its rare neoplastic L&H cells, which are dispersed in an abundant non-neoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected lymphocytic and histiocytic (L&H) lymphoma cells in comparison to normal and other malignant B cells, which indicates a relationship of L&H cells to and/or origin from germinal center B cells at transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell-rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype and deregulation of many apoptosis-regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive NF-κB activity and aberrant ERK signaling. Thus, these findings shed new light on the nature of L&H cells, revealed several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies. Experiment Overall Design: Analysis of differential gene expression in primary human lymphoma cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in comparison with primary lymphoma cells of classical Hodgkin lymphoma cells and other B-non-Hodgkin lymphoma (B-NHL) samples and subsets of non-neoplastic B lymphocytes isolated from blood or tonsils. 67 gene expression profiles were analysed.
2008-10-26 | E-GEOD-12453 | biostudies-arrayexpress
Project description:Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However, little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes. Gene expression analysis of Hodgkin lymphoma (cHL) and B-cell lines: Microarray data for three Hodgkin lymphoma cell lines (KM-H2, L1236, L428) and the B-cell line Namalwa that were published previously by our group (GEO accession GSE8388) were analyzed together with newly generated data for the B-cell lines SU-DHL4 and SU-DHL6. For all cell lines, RNA was isolated according to standard protocols (Qiagen, Hilden, Germany) and used for Affymetrix GeneChip hybridization (HG-U133A). Microarrays were normalized using RMA, and differential expression was calculated using moderated t-test. The gene expression profiles of the cell lines were generated in duplicates.
2011-05-05 | E-GEOD-21251 | biostudies-arrayexpress
Project description:To determine differential expression of miRNA in classical Hodgkin lymphoma diseased nodes compared to non-malignant lymph nodes, we used agilent microarray release 16 and quantile normalisation using Genespring GX software to quantify and compare miRNA expression..
2013-03-19 | GSE45264 | GEO
Project description:Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However, little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes.
2011-05-05 | GSE21251 | GEO