Project description:Primary central nervous system lymphoma(PCNSL) is a rare extra-nodal non-Hodgkin’s lymphoma and accounts for 3%-4% of central nervous system tumors. Recent studies have highlighted the importance of cerebrospinal fluid derived extracellular vesicles in PCNSL. Extracellular vesicles(EVs) are nanoscale vesicles with bilayer lipid membrane released by almost all cell types. EVs are present in body fluids, including urine, blood and CSF. Cerebrospinal fluid(CSF) is a colorless fluid that surrounds the brain and spinal cord and acts as lymph in the central nervous system. CSF-derived EVs contain proteins from neurons, oligodendrocytes, astrocytes and microglias. Studies of CSF EVs are mainly limited by the amount of EVs isolated from per milliliter of CSF and the volume of CSF acquired from one patient. Here, we provide a label-free quantitative phospho-proteome profiling of EVs separated from PCNSL and non-PCNSL CSF samples by an earlier introduced functional magnetic beads called EVTRAP together with highly sensitive timsTOF Pro.
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 .
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 .
Project description:This SuperSeries is composed of the following subset Series: GSE25297: Genome-wide gene expression comparison (primary central nervous system lymphoma (PCNSL) vs normal lymph node) GSE25298: Genomic aberrations in primary central nervous system lymphoma (PCNSL) Refer to individual Series
