TY - JOUR
T1 - Patient-derived xenograft mouse models to investigate tropism to the central nervous system and retina of primary and secondary central nervous system lymphoma
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 - Boerries, Melanie
AU - Illerhaus, Gerald
AU - Duyster, Justus
AU - Schueler, Julia
AU - von Bubnoff, Nikolas
N1 - Publisher Copyright:
© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
PY - 2023/4
Y1 - 2023/4
N2 - Aims: 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. Methods: We established a patient-derived central nervous system lymphoma xenograft mouse model and characterised xenografts derived from four primary and four 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. Results: 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. Conclusion: 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.
AB - Aims: 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. Methods: We established a patient-derived central nervous system lymphoma xenograft mouse model and characterised xenografts derived from four primary and four 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. Results: 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. Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=85153770764&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/d3cbbfe0-92f6-3a0d-9857-c191d062d467/
U2 - 10.1111/nan.12899
DO - 10.1111/nan.12899
M3 - Journal articles
C2 - 36879456
AN - SCOPUS:85153770764
SN - 0305-1846
VL - 49
SP - e12899
JO - Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
IS - 2
M1 - e12899
ER -