TY  - JOUR
AU  - Isbell, Lisa Kristina
AU  - Tschuch, Cordula
AU  - Doostkam, Soroush
AU  - Waldeck, Silvia
AU  - Andrieux, Geoffroy
AU  - Shoumariyeh, Khalid
AU  - Lenhard, Dorothee
AU  - Schaefer, Hans Eckart
AU  - Reinacher, Peter Christoph
AU  - Bartsch, Ingrid
AU  - Pantic, Milena
AU  - Vinnakota, Janaki Manoja
AU  - Kakkassery, Vinodh
AU  - Schorb, Elisabeth
AU  - Scherer, Florian
AU  - Frey, Anna Verena
AU  - Börries, Melanie
AU  - Illerhaus, Gerald
AU  - Duyster, Justus
AU  - Schueler, Julia
AU  - von Bubnoff, Nikolas
TI  - Patient-derived xenograft mouse models to investigate tropism to the central nervous system and retina of primary and secondary central nervous system lymphoma.
JO  - Neuropathology & applied neurobiology
VL  - 49
IS  - 2
SN  - 0305-1846
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2023-00461
SP  - e12899
PY  - 2023
N1  - 2023 Apr;49(2):e12899
AB  - How and why lymphoma cells home to the central nervous system and vitreoretinal compartment in primary diffuse large B-cell lymphoma of the central nervous system remain unknown. Our aim was to create an in vivo model to study lymphoma cell tropism to the central nervous system.We established a patient-derived central nervous system lymphoma xenograft mouse model and characterised xenografts derived from 4 primary and 4 secondary central nervous system lymphoma patients using immunohistochemistry, flow cytometry and nucleic acid sequencing technology. In reimplantation experiments, we analysed dissemination patterns of orthotopic and heterotopic xenografts and performed RNA sequencing of different involved organs to detect differences at the transcriptome level.We found that xenografted primary central nervous system lymphoma cells home to the central nervous system and eye after intrasplenic transplantation, mimicking central nervous system and primary vitreoretinal lymphoma pathology, respectively. Transcriptomic analysis revealed distinct signatures for lymphoma cells in the brain in comparison to the spleen as well as a small overlap of commonly regulated genes in both primary and secondary central nervous system lymphoma.This in vivo tumour model preserves key features of primary and secondary central nervous system lymphoma and can be used to explore critical pathways for the central nervous system and retinal tropism with the goal to find new targets for novel therapeutic approaches.
KW  - CNS tropism (Other)
KW  - patient-derived xenograft (Other)
KW  - primary and secondary central nervous system lymphoma (Other)
KW  - primary vitreoretinal lymphoma (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36879456
DO  - DOI:10.1111/nan.12899
UR  - https://inrepo02.dkfz.de/record/274155
ER  -