Gene expression profiling in DLBCL primary clinical samples
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE74266 | GEO | 2016/10/05
SECONDARY ACCESSION(S): PRJNA299613
REPOSITORIES: GEO
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Project description:Gene expression profiling was performed for 7 DLBCL primary clinical samples and assignment of activated B-cell-like(ABC)/germinal center B-cell-like (GCB) DLBCL classes, B-cell-associated gene signature (BAGS), and a probability of response to vincristine was performed for each sample. Diffuse large B-cell lymphoma (DLBCL) is a very heterogeneous malignant disease with diverse clinical presentation, outcome, and pathogenic mechanism. In order to better risk stratify patients there is a current need to find and validate new biomarkers of the disease. An alternatively spliced transcript of NOTCH3 missing exon 16 was identified and displayed prognostic and predictive biomarker potential.
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Project description:High expression of the FOXP1 transcription factor distinguishes the highly aggressive Activated B Cell (ABC) type of Diffuse Large B Cell Lymphoma (DLBCL) from the more indolent Germinal Center (GCB) DLBCL subtype and is correlated with poor prognosis. A genetic or functional role for FOXP1 in lymphomagenesis and/or tumor maintenance, however, remains unknown. Here, we report that sustained expression of FOXP1 is necessary for ABC DLBCL cell line survival. Genome-wide transcript profiling reveals that FOXP1 acts directly and indirectly by enforcing expression of known ABC DLBCL hallmarks, including the classical NF-kappaB survival pathway. Our data further suggest that FOXP1 maintains the ABC subtype distinction by repressing gene expression programs dominant in GCB DLBCL and supports a model in which the target of ABC DLBCL transformation is a transitory cell type en route from the germinal center B cell to the terminally differentiated plasma cell.
2015-12-01 | GSE64586 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) is currently divided into three main molecular subtypes, defined by gene expression profiling (GEP): Germinal Center B-cell like (GCB), Activated B-Cell like (ABC), and Primary Mediastinal B-cell Lymphoma (PMBL). DLBCL subtypes were determined according to patients' gene expression profiles.
2017-01-30 | GSE87371 | GEO
Project description:Multi-agent chemotherapy still represents the first-line standard-of-care treatment for diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adults. However, the clinicopathological and molecular heterogeneity of DLBCLs poses a major challenge in their successful therapy. At least two major subtypes, i.e. germinal center B-cell-like (GCB) and the aggressive activated B-cell-like (ABC) DLBCL, which differ both in their gene expression profile and in their mutation patterns, have been identified. Here we demonstrate a broad inhibitory effect of dimethyl fumarate (DMF) on the outgrowth of both DLBCL subtypes, even though the molecular basis for its efficacy differs between GCB and ABC DLBCL. Due to high expression of arachidonate 5-lipoxygenase in concert with low glutathione and glutathione peroxidase 4 levels, DMF induced lipid peroxidation and thus ferroptotic cell death in GCB DLBCL. In contrast, in ABC DLBCL inhibition of NF-κB and STAT3 activity essentially contributed to DMF-dependent cytotoxicity. Interestingly, the BCL-2 specific BH3 mimetic ABT-199 or an inhibitor of the ferroptosis suppressor protein 1 synergized with DMF treatment in inducing cell death in DLBCL cell lines. Collectively, our findings identify the established and approved drug DMF as a promising novel therapeutic option in the treatment of both GCB and ABC DLBCL.
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Project description:We studied 498 de-novo adult DLBCL cases, which had been diagnosed between January 2002 and October 2009, as part of the International DLBCL Rituximab-CHOP Consortium Program Study We perform global gene expression profiling from formalin fixed paraffin embedded 498 DLBCL tissues RNA by SPIA mediated microarray detection and identified the distinct subgroups of the disease within DLBCL, known as germinal-center-B-cell-like (GCB), activated B-cell-like (ABC), and unclassified DLBCL (UC).
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Project description:We performed array comparative genomic hybridization (aCGH) and gene expression profiling in 203 samples of diffuse large B cell lymphoma (DLBCL). By gene expression, at least three molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal B cell lymphoma (PMBL) can be distinguished. Combining gene expression profiling and aCGH, revealed copy number abnormalities that had strikingly different frequencies in the three molecular DLBCL subtypes. These data provide genetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways. Keywords: clinical history design The retrospective study included RNA and DNA extracted from 203 clinical samples.
2008-09-04 | E-GEOD-11318 | biostudies-arrayexpress
Project description:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with at least one-third of its patients not responding to the current chemotherapy regimen, R-CHOP. By gene expression profiling, patients with DLBCL can be categorized into two clinically relevant subtypes: activated B-cell (ABC) DLBCL and germinal center B-cell (GCB). Patients with ABC DLBCL have a worse prognosis, and are defined by chronic, overactive signaling through the B-cell receptor and NF-κB pathways. We examined the effects of the Src family kinase (SFK) inhibitor dasatinib in a panel of ABC and GCB DLBCL cell lines, and found that the ABC DLBCL cell lines are much more sensitive to dasatinib than the GCB DLBCL cell lines. However, using multiplexed inhibitor bead coupled to mass spectrometry (MIB/MS) kinome profiling competition and western blot analysis, both subtypes display inhibition of the SFKs in response to dasatinib after both short- and long-term treatment. MIB/MS analyses revealed several cell cycle kinases, including CDK4, CDK6, and the Aurora kinases, are inhibited by dasatinib treatment in the ABC DLBCL subtype, but not in the GCB DLBCL subtype. The present findings have important implications for the clinical use of dasatinib for the treatment of ABC DLBCL, either alone or in combination with other agents.
2018-12-14 | PXD009380 | Pride
Project description:We performed array comparative genomic hybridization (aCGH) and gene expression profiling in 203 samples of diffuse large B cell lymphoma (DLBCL). By gene expression, at least three molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal B cell lymphoma (PMBL) can be distinguished. Combining gene expression profiling and aCGH, revealed copy number abnormalities that had strikingly different frequencies in the three molecular DLBCL subtypes. These data provide genetic evidence that the DLBCL subtypes are distinct diseases that utilize different oncogenic pathways. Keywords: clinical history design
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Project description:miRNA profiling of human Diffuse Large B Cell Lymphoma (DLBCL) cell lines derived from the two main subtypes of this disease: Activated B Cell like (ABC-DLBCL) and Germinal Center B cell like (GCB-DLBCL), analyzing the 711 human miRNAs present in miRBase V10.0. Five ABC-like DLBCL cell lines (RIVA, Oci-Ly3, Oci-Ly10, HBL1 and U2932) and three GCB-like DLBCL cell lines (Oci-Ly7, Oci-Ly19 and SUDHL-6) were cultured in IMDM (Cellgro) with 20% human plasma, 1% penicillin/streptomycin/L-glutamine (Cellgro,) and 0,2% beta mercaptoethanol (Invitrogen). Total RNA was extracted from cell pellets using the mirVana™ miRNA Isolation Kit (Ambion), and sent to LC Sciences facility for microarray hybridization using microfluidics technology. FirstChoice® Human Skeletal Muscle Total RNA (Ambion) was used as common reference for all hybridizations. Background substracted and normalized data from each channel was used to calculate log ratios sample/reference. Keywords: miRNA profiling
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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