Analysis of gene expression signatures for primary vitreo retinal lymphoma
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ABSTRACT:
PROVIDER: PRJNA525342 | ENA |
REPOSITORIES: ENA
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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 .
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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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