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Primary CNS lymphoma B cell receptors recognize CNS proteins

ABSTRACT: Primary lymphoma of the central nervous system (PCNSL) is a diffuse large B cell lymphoma confined to the CNS. In order to elucidate its peculiar organ tropism, we generated recombinant antibodies (recAb) identical with the BCR of a series of 23 PCNSL from immunocompetent patients. While none of the recAb showed self-reactivity upon testing with common autoantigens, they recognized 1547 proteins present on a large-scale protein microarray. Interestingly, proteins recognized by the recAb are physiologically expressed by CNS neurons (GRINL1A, centaurin-α, BAIAP2). Furthermore, 87% (20/23) of the recAb including all antibodies derived from IGHV4 34 using PCNSL recognized galectin-3, which was upregulated on microglia/macrophages, astrocytes, and cerebral endothelial cells upon CNS invasion by PCNSL. Thus, PCNSL Ig may recognize CNS proteins as self-antigens. Their interaction may contribute to BCR signaling with sustained NF-κB activation and, ultimately, may foster tumor cell proliferation and survival. These data may also explain, at least in part, the affinity of the tumor cells of PCNSL to the CNS. Recombinant antibodies (recAb) identical with the BCR of a series of 23 PCNSL from immunocompetent patients.

ORGANISM(S): Homo sapiens

SUBMITTER: Manuel Montesinos-Rongen

PROVIDER: E-GEOD-61556 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Primary CNS lymphoma B cell receptors recognize CNS proteins

Project description:Primary lymphoma of the central nervous system (PCNSL) is a diffuse large B cell lymphoma confined to the CNS. In order to elucidate its peculiar organ tropism, we generated recombinant antibodies (recAb) identical with the BCR of a series of 23 PCNSL from immunocompetent patients. While none of the recAb showed self-reactivity upon testing with common autoantigens, they recognized 1547 proteins present on a large-scale protein microarray. Interestingly, proteins recognized by the recAb are physiologically expressed by CNS neurons (GRINL1A, centaurin-α, BAIAP2). Furthermore, 87% (20/23) of the recAb including all antibodies derived from IGHV4 34 using PCNSL recognized galectin-3, which was upregulated on microglia/macrophages, astrocytes, and cerebral endothelial cells upon CNS invasion by PCNSL. Thus, PCNSL Ig may recognize CNS proteins as self-antigens. Their interaction may contribute to BCR signaling with sustained NF-κB activation and, ultimately, may foster tumor cell proliferation and survival. These data may also explain, at least in part, the affinity of the tumor cells of PCNSL to the CNS.

2015-07-01 | GSE61556 | GEO

Xenograft mouse model to investigate tropism to the CNS and retina in primary central nervous system lymphoma (first batch)

Project description:Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare, extranodal lymphoma. Primary vitreo-retinal lymphoma (PVRL) occurs in 15-25% of PCNSL. CNS involvement also occurs in systemic diffuse large B-cell lymphoma, termed secondary central nervous system lymphoma (SCNSL). Despite intensive treatment, patient outcomes are poor when compared to DLBCL without CNS involvement. How and why lymphoma cells home to the CNS and vitreo-retinal compartment remains unknown. In vivo models to study lymphoma cell tropism are urgently needed. We therefore established and characterized 3 primary and 4 secondary patient-derived CNS lymphoma xenograft mouse models using immunohistochemistry, flow cytometry and nucleic acid sequencing technology. In spleen reimplantation experiments, we characterized the dissemination pattern of orthotopic and heterotopic xenografts and performed RNA sequencing to detect differences on the transcriptome level. Moreover, we found that lymphoma cells in PCNSL xenografts home to the eye after intrasplenal implantation in around 60% of cases, similar to PVRL. This in vivo tumor model preserves key features of this rare lymphoma entity and can be used to explore pathways that are critical for CNS and retinal tropism with the goal to find potential new targets for novel therapeutic approaches .

2023-10-11 | GSE189822 | GEO

Xenograft mouse model to investigate tropism to the CNS and retina in primary central nervous system lymphoma (second batch)

Project description:Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare, extranodal lymphoma. Primary vitreo-retinal lymphoma (PVRL) occurs in 15-25% of PCNSL. CNS involvement also occurs in systemic diffuse large B-cell lymphoma, termed secondary central nervous system lymphoma (SCNSL). Despite intensive treatment, patient outcomes are poor when compared to DLBCL without CNS involvement. How and why lymphoma cells home to the CNS and vitreo-retinal compartment remains unknown. In vivo models to study lymphoma cell tropism are urgently needed. We therefore established and characterized 2 primary and 2 secondary patient-derived CNS lymphoma xenograft mouse models using immunohistochemistry, flow cytometry and nucleic acid sequencing technology. In spleen reimplantation experiments, we characterized the dissemination pattern of orthotopic and heterotopic xenografts and performed RNA sequencing to detect differences on the transcriptome level. Moreover, we found that lymphoma cells in PCNSL xenografts home to the eye after intrasplenal implantation in around 60% of cases, similar to PVRL. This in vivo tumor model preserves key features of this rare lymphoma entity and can be used to explore pathways that are critical for CNS and retinal tropism with the goal to find potential new targets for novel therapeutic approaches .

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Pathway analysis of primary central nervous system lymphoma (PCNSL)

Project description:Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B cell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a “CNS signature.” Keywords: disease state analysis

2008-05-10 | GSE11392 | GEO

Integrated genetic analysis of primary CNS lymphoma

Project description:Immunodeficiency-related Epstein-Barr-virus-positive (EBV+) primary CNS lymphoma (PCNSL) represents a distinct clinical entity with an inferior prognosis compared to EBV--disease. Genetic alterations that drive EBV-related CNS lymphomagenesis remain unclear precluding targeted therapies. In this study, we performed whole-exome sequencing of 5 paired (tumor and germline control) and 13 unpaired (tumor only) EBV+ PCNSL as well as 2 EBV- controls.

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Gene expression profiling suggests PCNSL to be derived from a late germinal center B cell.

Project description:To characterize the molecular origin of primary lymphomas of the central nervous system (PCNSL), 21 PCNSL of immunocompetent patients were investigated by microarray-based gene expression profiling. Comparison of the transcriptional profile of PCNSL with various normal and neoplastic B cell subsets demonstrated PCNSL (i) to display gene expression patterns most closely related to late germinal center B cells, (ii) to display a gene expression profile similar to systemic diffuse large B cell lymphomas (DLBCL), and (iii) to be in part assigned to the activated B cell-like (ABC) or the germinal center B cell-like (GCB) subtype of DLBCL. Keywords: PCNSL – DLBCL – gene expression profiling

2007-12-16 | GSE6047 | GEO

Kinesin-associated RNA: RNA co-immunoprecipitated with Kinesin IP vs RNA from Aplysia CNS

Project description:Whole genome transcriptional profiling is used to identify ESTs found in RNA co-immunoprecipitated from Aplysia CNS with antibodies against Aplysia Kinesin Heavy Chain (ApKHC) RNA derived from Aplysia CNS served as control in the opposite channel. Custom Aplysia EST array to probe the samples was designed and ordered from Agilent.

2013-04-26 | GSE30386 | GEO

Array-based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non-CNS diffuse large B-cell lymphomas

Project description:Genome wide DNA methylation profiling of 26 primary central nervous system lymphomas (PCNSL). The Illumina Infinium HumanMethylation 450 BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in PCNSL samples.

2019-10-01 | GSE120357 | GEO

Kinesin-associated RNA: RNA co-immunoprecipitated with Kinesin IP vs RNA from Aplysia CNS

2013-04-26 | E-GEOD-30386 | biostudies-arrayexpress

Gene Expression and HD-SNP6.0 data from Primary Testicular (PTL), Primary Central Nervous System Lymphoma (PCNSL) and Primary Mediastinal B-cell Lymphoma (PMLBCL)

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2015-12-31 | E-GEOD-61578 | biostudies-arrayexpress

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