Subtype Specific Addiction of the Activated B Cell Subset of Diffuse Large B Cell Lymphoma to FOXP1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE63257 | GEO | 2016/01/03
SECONDARY ACCESSION(S): PRJNA267114
REPOSITORIES: GEO
Similar Datasets
Project description:Genome wide transcript and target gene profiling reveal that FOXP1 acts directly and indirectly by enforcing known ABC-DLBCL hallmarks, including Chronically Activated B cell receptor Signaling (CABS) and the classical NF-κB survival pathway. Our data further suggest that FOXP1 maintains ABC-subtype distinction by repressing gene expression programs dominant in GCB-DLBCL and support a model in which the normally transitory B cell plasmablast is the target of ABC-DLBCL transformation. ChIP sequenicng was performed for the FOXP1 transcription factor in DLBCL cell lines. Input was sequenced and used as a control.
2016-07-05 | E-GEOD-63257 | biostudies-arrayexpress
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: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: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:Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, including two main molecular subtypes termed activated B cell-like (ABC) and germinal center B cell-like (GCB). ABC DLBCL is less curable and identification of new molecular targets is needed for the development of effective therapeutic agents. Here, we focused on EGR1, a transcription factor that is regulated by the B cell receptor and JAK1/STAT3 signaling pathway in ABC DLBCL. ChIP-Seq and RNA-Seq analyses revealed that gene regulation by EGR1 in ABC DLBCL accentuates multiple oncogenic pathways, including MYC and E2F, while dampening the lethal type I IFN pathway.
2021-08-06 | GSE123291 | GEO
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 have developed a novel immunocompetent multi-lesion mouse model of activated B cell diffuse large B-cell lymphoma (ABC-DLBCL; the pBIC mice) that recapitulates relatively fast the molecular, cellular and tumor microenvironment of aggressive human ABC-DLBCL. We demonstrate that perturbed p53 signaling cooperates with constitutive NF-kB activation in GC-experienced plasmablasts with blocked terminal differentiation to promote lymphomagenesis and tumor progression through triggering downstream intracellular molecular addictions (e.g. deregulating Foxp1 and AID pathways) and intercellular immunosuppressive signals for evading anti-tumoral responses (e.g. MHC-II antigen presentation and deregulating PD-L1/PD-1 immune checkpoint). Our immunocompetent ABC-DLBCL murine model provides in vivo evidence that PD-1 blockade cooperates with anti-CD20-based current standard-of-care therapy to reshape the immunosuppressive TME and facilitate long-term anti-tumoral responses. Therefore, our results support that immune checkpoints may hold promising therapeutic potential in ABC-DLBCL.
2019-04-19 | GSE116289 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) comprises molecularly distinct subgroups such as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCLs. We previously reported that CD5(+) and CD5(-)CD10(+) DLBCL constitute clinically relevant subgroups. To determine whether these 2 subgroups are related to ABC and GCB DLBCLs, we analyzed the genomic imbalance of 99 cases (36 CD5(+), 19 CD5(-)CD10(+), and 44 CD5(-)CD10(-)) using array-based comparative genomic hybridization (CGH). Forty-six of these cases (22 CD5(+), 9 CD5(-)CD10(+), 1 CD5 (-), and 14 CD5(-)CD10(-)) were subsequently subjected to gene-expression profiling, resulting in their division into 28 ABC (19 CD5(+) and 9 CD5(-)CD10(-)) and 18 GCB (3 CD5(+), 7 CD5(-)CD10(+), and 8 CD5(-)CD10(-)) types. A comparison of genome profiles of distinct subgroups of DLBCL demonstrated that (1) ABC DLBCL is characterized by gain of 3q, 18q, and 19q and loss of 6q and 9p21, and GCB DLBCL is characterized by gain of 1q, 2p, 7q, and 12q; (2) the genomic imbalances characteristic of the CD5(+) and CD5(-)CD10(+) groups were similar to those of the ABC and GCB types, respectively. These findings suggest that CD5(+) and CD5(-)CD10(+) subgroups are included, respectively, in the ABC and GCB types. Finally, when searching for genomic imbalances that affect patients' prognosis, we found that 9p21 loss (p16(INK4a) locus) marks the most aggressive type of DLBCL. Expression profiles in 46 patients with DLBCL and 8 for normal lymph node biopsy samples.
2009-07-10 | E-GEOD-16920 | biostudies-arrayexpress
Project description:The goal of this study is to identify the transcriptome differences between the two major subtypes of diffuse large B cell lymphoma (DLBCL). DLBCL is the most common form of non-Hodgkin’s lymphoma and has two major subtypes: germinal center B-cell-like (GCB) and activated B-cell-like (ABC). When compared to the GCB form, ABC lymphomas respond much more poorly to current therapies. To investigate how gene expression changes might contribute to this aggressive phenotype, we have used RNA-Seq to profile the whole transcriptome in 8 DLBCL cell lines (4 GCB subtype, 4 ABC) that are derived from patient tumors. 1,545 genes are differentially expressed between subtypes (FDR < 0.05), approximately 7% of the transcriptome. The vast majority of these genes (81%, n = 1251) are more highly expressed in the ABC cell lines. In contrast, only 294 genes (19%) are more highly expressed in the GCB cell lines. Half (n = 765) of the genes with greater ABC subtype expression demonstrate very low read counts (< 5) in the GCB cell types. Conversely, only 21 genes that are more highly expressed in GCB are unique to that subtype. The prevalence of such “on/off” genes indicates that the major differences between ABC and GCB DLBCL are due almost exclusively to additional gene expression in ABC, rather than the two subtypes having divergent but equally active genetic programs. Measurement and comparison of gene expression in 8 cell lines representing the 2 subtypes of DLBCL. 4 cell lines are subtyped as ABC and 4 are subtyped as GCB. 2 replicates are present for each cell line. (Cell line OCI-Ly19 was not included in the analysis because its gene expression clustered in between the subtypes, probably due to its EBV+ status. However, its sequencing runs have been included for completeness.)
2013-12-16 | E-GEOD-50721 | biostudies-arrayexpress