Epigenetic priming using low-dose 5-azazcytidine in diffuse large B-cell lymphoma (MBD-Seq)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE190320 | GEO | 2022/09/27
REPOSITORIES: GEO
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Project description:RNA sequencing of low-dose 5-azacytidine treated and PBS treated DLBCL cell lines to measure transcriptional changes in gene and endogenous retrovirus expression
2022-09-27 | GSE190319 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumors. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumors of DLBCL patients, apparently reflecting the variation in tumor proliferation rate, host response and differentiation state of the tumor. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal center B cells ('germinal center B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal center B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumors on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. This study is described more fully in Alizadeh AA et al.(2000) Nature 403:503-11
2002-06-27 | E-GEOD-60 | biostudies-arrayexpress
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumors. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumors of DLBCL patients, apparently reflecting the variation in tumor proliferation rate, host response and differentiation state of the tumor. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal center B cells ('germinal center B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal center B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumors on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. This study is described more fully in Alizadeh AA et al.(2000) Nature 403:503-11 Keywords: other
2002-06-27 | GSE60 | GEO
Project description:To identify differentially expressed genes regulated by FOXP1 in DLBCL cells via gene expression profiling of GCB-DLBCL (DB, K422) and ABC-DLBCL (OCI-Ly3, HBL-1) cell lines treated with siRNA targeting FOXP1 or non-silencing siRNA control.
2015-10-27 | GSE71526 | GEO
Project description:Despite recent therapeutic improvements, the clinical course of diffuse large B-cell lymphoma (DLBCL) still differs considerably among patients. We conducted this retrospective multi-centre study to evaluate the impact of genomic aberrations detected using a high-density genome wide-single nucleotide polymorphism-based array on clinical outcome in a population of DLBCL patients treated with R-CHOP-21 (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 d). 167 DNA samples were analysed using the GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their impact on the clinical course of 124 patients treated with R-CHOP-21. Unsupervised clustering was performed to identify genetically related subgroups of patients with different clinical outcomes. Twenty recurrent genetic lesions showed an impact on the clinical course. Loss of genomic material at 8p23.1 showed the strongest statistical significance and was associated with additional aberrations, such as 17p- and 15q-. Unsupervised clustering identified five DLBCL clusters with distinct genetic profiles, clinical characteristics and outcomes. Genetic features and clusters, associated with a different outcome in patients treated with R-CHOP, have been identified by arrayCGH. DNA copy number profiling by SNP array.
2009-04-01 | GSE15127 | GEO
Project description:Gene expression profiling was performed for 21 DLBCL patients. Based on the gene expression profile, each patient was classified into the molecular subclasses: Activated B-cell-like (ABC)/Germinal-center B-cell-like (GCB). A major clinical challenge of diffuse large B-cell lymphoma (DLBCL) is that up to 40% of patients have refractory disease or relapse after initial response to therapy, due to drug-specific molecular resistance. The purpose of the present study was to investigate microRNA (miRNA) involvement in vincristine resistance in DLBCL which was pursued by functional in vitro analysis in DLBCL cell lines and by clinical analysis of DLBCL patients treated with R-CHOP. MiR-155 was documented to be directly linked to vincristine response in DLBCL cell lines and association between miR-155 and ABC/GCB subclasses and clinical outcome was investigated in primary DLBCL samples.
2019-12-31 | GSE109027 | GEO
Project description:To identify differentially expressed genes regulated by FOXP1 in DLBCL cells via gene expression profiling of GCB-DLBCL (DB, K422) and ABC-DLBCL (OCI-Ly3, HBL-1) cell lines treated with siRNA targeting FOXP1 or non-silencing siRNA control. Two GCB-DLBCL (DB, K422) and two ABC-DLBCL (OCI-Ly3, HBL-1) cell lines were each treated separately with two independent siRNA oligonucleotides targeting FOXP1 (siFOXP1_308, siFOXP1_309) or non-silencing siRNA (siCtrl). Biological replicates derived from three independent experiments were obtained, RNA-extracted and subsequently hybridized into a human microarray platform for gene expression profiling.
2015-10-27 | E-GEOD-71526 | biostudies-arrayexpress
Project description:Diffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.
2019-11-23 | GSE140882 | GEO
Project description:Molecular pathogenesis of posttransplant (PT) lymphoproliferative disorder, including the most prevalent diffuse large B cell lymphoma (DLBCL), is largely unknown. We have recently showed that Epstein-Barr Virus (EBV)+ and EBV- PT-DLBCL are biologically different, but gene expression profile of the latter lymphoma is similar to that of immunocompetent (IC) DLBCL. To validate these findings on a genomic level, we performed array CGH analysis of 21 EBV+ and 6 EBV- PT-DLBCL, and 11 control IC-DLBCL. Genomic and transcriptomic data were subsequently integrated. Notably, EBV+ and EBV- PT-DLBCL revealed only one shared recurrent imbalance, while EBV- PT-DLBCL displayed at least 10 aberrations recurrent in IC-DLBCL, among others gain of 3/3q and 18q, and loss of 6q23/TNFAIP3 and 9p21/CDKN2A. EBV+ PT-DLBCL showed distinct aberrations, including the most prevalent gain/amplification of 9p24.1 targeting PDCD1LG2/PDL2. Significant differential representation/expression of 3p13/FOXP1 and 9p21/CDKNA2 in EBV+ PT-DLBCL when compared with EBV- PT-/IC-DLBCL, suggests that the oncogene FOXP1 and the tumor suppressor gene CDKNA2 are not implicated in pathogenesis of EBV+ PT-DLBCL. In summary, genomic profiling of PT-/IC-DLBCL confirmed biological distinctness of EBV+ and EBV- PT-DLBCL, and relationship between EBV- PT-DLBCL and IC-DLBCL. These findings support the hypothesis that EBV- PT-DLBCL are coincidental lymphomas in transplant recipients
2015-06-02 | GSE69440 | GEO
Project description:Intrinsic resistance of lymphoma cells to apoptosis is a probable mechanism causing chemotherapy resistance and eventual fatal outcome in patients with diffuse large B cell lymphomas (DLBCL). We investigated whether microarray expression profiling of apoptosis related genes predicts clinical outcome in 46 patients with primary nodal DLBCL. Unsupervised cluster analysis using genes involved in apoptosis (N=246) resulted in 3 separate DLBCL groups partly overlapping with GCB versus ABC like phenotype. One group with poor clinical outcome was characterized by high expression levels of pro-and anti-apoptotic genes involved in the intrinsic apoptosis pathway. A 2nd group, also with poor clinical outcome, was characterized by high levels of apoptosis inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. The 3rd group showing a favourable outcome was characterized by low expression levels of genes characteristic for both other groups. Our results suggest that chemotherapy refractory DLBCL are characterized either by an intense cellular cytotoxic immune response or by constitutive activation of the intrinsic mediated apoptosis pathway with concomitant downstream inhibition of this apoptosis pathway. Consequently, strategies neutralizing the function of apoptosis-inhibiting proteins might be effective as alternative treatment modality in part of chemotherapy refractory DLBCL. Keywords: expression profiling B lymphomas
2006-12-08 | GSE3892 | GEO