SMAD1 promoter hypermethylation and lack of SMAD1 expression in Hodgkin Lymphoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE147387 | GEO | 2020/04/06
REPOSITORIES: GEO
Similar Datasets
Project description:SMAD1 promoter hypermethylation and lack of SMAD1 expression in Hodgkin Lymphoma
| PRJNA614470 | ENA
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:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL (LP-DLBCL) by gene expression profiling (GEP). GEP revealed an inflammatory signature pinpointing to a specific host response. In a coculture model resembling this host response, DEV tumor cells showed an impaired growth behavior. Mechanisms involved in the reduced tumor cell proliferation included a downregulation of MYC and its target genes. Lack of MYC expression was also confirmed in 12/16 LP-DLBCL by immunohistochemistry. Furthermore, CD274/PD-L1 was upregulated in tumor cells after coculture with T cells or monocytes and its expression was validated in 12/19 cases of LP-DLBCL. Thereby, our data provide new insights into the pathogenesis of LP-DLBCL and a concrete explanation of the relatively low tumor cell content. Moreover, our results suggest that treatment of these patients with checkpoint inhibitors may enhance an already ongoing host response in these patients.
2017-06-12 | GSE84688 | GEO
Project description:Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL (LP-DLBCL) by gene expression profiling (GEP). GEP revealed an inflammatory signature pinpointing to a specific host response. In a coculture model resembling this host response, DEV tumor cells showed an impaired growth behavior. Mechanisms involved in the reduced tumor cell proliferation included a downregulation of MYC and its target genes. Lack of MYC expression was also confirmed in 12/16 LP-DLBCL by immunohistochemistry. Furthermore, CD274/PD-L1 was upregulated in tumor cells after coculture with T cells or monocytes and its expression was validated in 12/19 cases of LP-DLBCL. Thereby, our data provide new insights into the pathogenesis of LP-DLBCL and a concrete explanation of the relatively low tumor cell content. Moreover, our results suggest that treatment of these patients with checkpoint inhibitors may enhance an already ongoing host response in these patients.
2017-06-12 | GSE84464 | GEO
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.
2008-10-01 | GSE12453 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE25986: Gene expression profiling of cell lines derived from classical Hodgkin lymphoma GSE25987: Gene expression profiling of Hodgkin lymphoma cell line KMH2: Comparison of CIITA-BX648577 knockdown cultures with non-silencing controls GSE25989: Copy number analysis of Hodgkin lymphoma cell lines KM-H2 and L-428 Refer to individual Series *** This submission represents the microarray gene expression and microarray copy number components of the study
2010-12-11 | E-GEOD-25990 | biostudies-arrayexpress
Project description:Tumor cells were microdissected from frozen sections of NLPHL and THRLBCL. RNA was amplified using the NUGEN WT-Ovation-One-direct-Kit. Samples were compared to tonsilar germinal center CD77 B cells.
2013-12-01 | GSE47044 | GEO
Project description:Leukotriene (LT) D4 contributes to aberrant cytokine networks of classical Hodgkin lymphonoma, This study has investigated LTD4 induced gene expression and pathway in Hodgkin lymphonma cell line L1236.
2015-01-01 | GSE43855 | GEO
Project description:An Hodgkin Lymphoma cell line have been treated with an LNA inhibitor for miR-9 or with a scramble LNA to identify miR-9 regulated pathways that could be important for Hodgkin Lymphoma pathogenesis.
2012-05-02 | GSE27529 | GEO
Project description:We produced and analyzed the transcriptomic profiles of 40 lymphoma patients. We used microarrays to compare the global gene expression profile between the different subtypes. These samples were analyzed with a tool predictive of immune escape mechanisms previously developped, IEGS33. Depending on lymphoma subtype, different immune escape signatures can be observed. Therapeutic based on PD-1/PD-L1 blockade shows promising results in Hodgkin lymphoma (HL) and in some diffuse large B-cell lymphoma (DLBCL) patients but biomarkers predicting therapeutic response are still lacking. To gain understanding on the overall immune-escape (IE) mechanism, we recently developed a tool to score the transcriptional IE hallmarks in lymphoma samples and identified four stages of cancer immune-editing in DLBCL that correlated with overall survival. Through this method, we described here the IE profiles in HL and DLBCL from a meta-analysis of large series of microarrays. We observed that HL clustered together at the late equilibrium-early escape stage of cancer immune-editing with significant enrichment of genes involved in IE and T-cell activation as compared to DLBCL. Deconvolution of transcriptomes and immunohistochimistry showed that HL had higher CD3+ and CD4+ T-cells than all DLBCL and shared high abundance of CD8+ T-cells with DLBCL ABC and low infiltrates of CD68+CD163+ macrophages with DLBCL GC. HL and DLBCL shared the same cellular distribution of PD-1 and TIM3 staining but HL exhibited a higher expression of PD-L1 in tumor cells as well as LAG3 overexpression in ME as compared to DLBCL. Finally, our bioinformatic tools based on IEGS33 and T cell activation scores as global approach of immune escape mechanisms help to investigate in details the ME of HL. This method may be useful tool to identify HL as well as DLBCL patients who better benefit from immunotherapy strategies.
2018-12-26 | GSE120124 | GEO