Acquisition of a Glycosylated B-Cell Receptor Drives Follicular Lymphoma Towards a Dark Zone Phenotype
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233953 | GEO | 2023/07/24
REPOSITORIES: GEO
Similar Datasets
Project description: Not available
| S-EPMC10561043 | biostudies-literature
Project description:Acquisition of a Glycosylated B-Cell Receptor Drives Follicular Lymphoma Towards a Dark Zone Phenotype
| PRJNA978638 | ENA
Project description:Functional discrimination between normal centroblast and centrocyte obtained from human inflamed tonsils after cell sorting. We used microarrays to detail the segregation between these two B cell subsets
2009-06-04 | GSE15271 | GEO
Project description:Functional discrimination between normal centroblast and centrocyte obtained from human inflamed tonsils after cell sorting. We used microarrays to detail the segregation between these two B cell subsets Flow cytometry analysis was done on human germinal center B cells and cell subsets, i.e. CXCR4pos and CXCR4neg, sorted before RNA extraction and hybridization on Affymetrix microarrays. Both B-cell subsets where obtained from an identical tonsil allowing paired statistical analysis.
2009-06-04 | E-GEOD-15271 | biostudies-arrayexpress
Project description:Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
2015-03-24 | GSE56313 | GEO
Project description:Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
2015-03-24 | GSE56314 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below: GSE56313 and GSE56314 Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
2015-03-24 | GSE56315 | GEO
Project description:Efficient generation of germinal center (GC) responses requires directed movement of B cells between distinct microenvironments underpinned by specialized B cell-interacting reticular cells (BRCs). How BRCs are reprogrammed to cater to the developing GC remains unclear, and studying this process is largely hindered by incomplete resolution of the cellular composition of the B cell follicle. Here we used genetic targeting of Cxcl13-expressing cells to define the molecular identity of the BRC landscape. Single-cell transcriptomic analysis revealed that BRC subset specification was predetermined in the primary B cell follicle. Further topological remodeling of light and dark zone follicular dendritic cells required CXCL12-dependent crosstalk with B cells and dictated GC output by retaining B cells in the follicle and steering their interaction with follicular helper T cells. Together, our results reveal that poised BRC-defined microenvironments establish a feed-forward system that determines the efficacy of the GC reaction.
| S-EPMC7610477 | biostudies-literature
Project description:SMARCA4 encodes one of two mutually-exclusive ATPase subunits in the Brg/Brm associated factor (BAF) complex that is recruited by transcription factors to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ~30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency is able to cooperate with Myc over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of transcription factors that are activated in centrocytes to drive GC-exit, including SPI1, IRF4 and NFκB. Loss of activity for these factors drove aberrant Bcl6 activity within murine centrocytes and human BL cells. Smarca4 therefore facilitates chromatin accessibility for transcription factors that shape centrocyte trajectories, and loss of fine-control of these programs biases towards centroblast cell-fate and GC hyperplasia.
2024-02-05 | GSE239937 | GEO
Project description:SMARCA4 encodes one of two mutually-exclusive ATPase subunits in the Brg/Brm associated factor (BAF) complex that is recruited by transcription factors to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ~30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperates with Myc over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of transcription factors that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family and NFκB. Loss of activity for these factors phenocopied aberrant Bcl6 activity within murine centrocytes and human BL cells. Smarca4 therefore facilitates chromatin accessibility for transcription factors that shape centrocyte trajectories, and loss of fine-control of these programs biases towards centroblast cell-fate and GC hyperplasia.
2024-02-05 | GSE254907 | GEO