Abstract
Objectives: How and why lymphoma cells lodge in the central nervous system and in the vitreoretinal compartment in primary diffuse large B-cell lymphoma of the central nervous system remains unknown. Our aim was to create an in vivo model to study the tropism of lymphoma cells towards the central nervous system. Methods: We constructed a mouse xenograft model for patients' own central nervous system lymphomas and characterized xenografts from four patients with primary and four secondary central nervous system lymphomas using immunohistochemistry, flow cytometry, and nucleic acid sequencing technology. In reimplantation experiments, we analyzed propagation 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 return to the central nervous system and eye after intrasplenic transplantation, mimicking central nervous system and primary vitreoretinal lymphoma pathology, respectively. Transcriptomic analysis revealed clear signatures for lymphoma cells in the brain compared to the spleen, and a low level of overlap of genes commonly regulated in primary and secondary central nervous system lymphomas. Conclusion: This in vivo tumor model preserves key features of primary and secondary central nervous system lymphoma and can be used to explore critical pathways to the central nervous system and retinal trophism with the aim of finding new targets for new therapeutic approaches.
Ursprache | English |
---|---|
item number | e12899 |
Daily | Neuropathology and Applied Neurobiology |
Volume | 49 |
issue number | 2 |
ISSN | 0305-1846 |
Two | |
release status | Published -04.2023 |
Research areas and centers
- Forschungsgebiet: Luebeck Integrated Oncology Network (LION)
- Centers: University Cancer Center Schleswig-Holstein (UCCSH)
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Isbell , LK , Tschuch , C , Doostkam , S , Waldeck , S , Andrieux , G , Shoumariyeh , K , Lenhard , D , Schaefer , HE , Reinacher , PC , Bartsch , I , Pantic , M , Vinnakota , JM ., Kakkassery, V., Schorb, E., Scherer, F., Frey, A. V., Boerries, M., Illerhaus, G., Duyster, J., ... by Bubnoff, N.(2023).Patient-derived xenograft mouse models to study the central nervous system and retinal tropism of primary and secondary central nervous system lymphomas.Neuropathology and Applied Neurobiology,49(2), [e12899].https://doi.org/10.1111/nan.12899
Isbell, Lisa Christina; Tschuch , Chordula ; Doostkam, Soroush et al. /Patient-derived xenograft mouse models to study the central nervous system and retinal tropism of primary and secondary central nervous system lymphomas. Em:Neuropathology and Applied Neurobiology. 2023; Wow. 49, No. 2.
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title = "Patient-derived mouse xenograft models to study the central nervous system and retinal tropism of primary and secondary central nervous system lymphomas",
abstract = “Objectives: How and why lymphoma cells lodge in the central nervous system and in the vitreoretinal compartment in primary diffuse large B-cell lymphoma of the central nervous system remains unknown. Our aim was to create an in vivo model to study the tropism of lymphoma cells into the central nervous system Characterized by immunohistochemistry, flow cytometry and nucleic acid sequencing technology. In reimplantation experiments, we analyzed propagation patterns of orthotopic and heterotopic xenografts and performed RNA sequencing of different involved organs to detect differences at the transcriptome, central nervous system, and primary vitreoretinal lymphoma levels, respectively. Transcriptomic analysis revealed clear signatures for lymphoma cells in the brain compared to the spleen, and a low level of overlap of genes commonly regulated in primary and secondary central nervous system lymphomas. Conclusion: This in vivo tumor model preserves key features of primary and secondary central nervous system lymphoma and can be used to explore critical pathways to the central nervous system and retinal trophism with the aim of finding new targets for new therapeutic approaches.
autor = „Isbell, Cordula Tschuch, Soroush Doostkam, Silvia Waldeck, Geoffroy Andrieux, Khalid Shoumariyeh, Dorothee Lenhard, Schaefer, Reinacher, Peter Christoph, [Janaki Manoja], Vinodh Kakkassery, Elisabeth Schorb, Florian Scherer, Frey, Melanie Boerries, Gerald Illerhaus, Justus Duyster, Julia Schueler, von Bubnoff, Nikolas“
note = "Editor's copyright: {\textcopyright} 2023 The Authors. Neuropathology and Applied Neurobiology, published by John Wiley & Sons Ltd on behalf of the British Neuropathological Society.”,
again = "2023",
month = April,
two = "10.1111/in.12899",
language="English",
volume = "49",
Journal = "Neuropathology and Applied Neurobiology",
issn = „0305-1846“,
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Isbell , LK , Tschuch , C , Doostkam , S , Waldeck , S , Andrieux , G , Shoumariyeh , K , Lenhard , D , Schaefer , HE , Reinacher , PC , Bartsch , I , Pantic , M , Vinnakota , JM, Kakkassery, V, Schorb, E, Scherer, F, Frey, AV, Boerries, M, Illerhaus, G, Duyster, J, Schueler, J2023, 'Patient-derived xenograft mouse models to study the central nervous system and retinal tropism of primary and secondary central nervous system lymphomas',Neuropathology and Applied Neurobiology, Bd. 49, Nr. 2, e12899.https://doi.org/10.1111/nan.12899
Patient-derived xenograft mouse models to study the central nervous system and retinal tropism of primary and secondary central nervous system lymphomas./Isbell, Lisa Christina; Tschuch, Chordula; Doostkam, Soroush et al.
Em:Neuropathology and Applied Neurobiology, Bd. 49, Nr. 2, e12899, 04.2023.
search result:contribution to the journal›newspaper article›To search›Peer-Review
YOU - DIA
T1 - Patient-derived xenograft mouse models to study the central nervous system and retinal tropism of primary and secondary central nervous system lymphomas
AU – Isbell, Lisa Kristina
AU - Tschuch, Córdula
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 – Editora Copyright: © 2023 The Authors. Neuropathology and Applied Neurobiology, published by John Wiley & Sons Ltd on behalf of the British Neuropathological Society.
Fiscal year – 2023/4
A1 – 2023/4
N2 - Objectives: How and why lymphoma cells lodge in the central nervous system and in the vitreoretinal compartment in primary diffuse large B-cell lymphoma of the central nervous system remains unknown. Our aim was to create an in vivo model to study the tropism of lymphoma cells towards the central nervous system. Methods: We constructed a mouse xenograft model for patients' own central nervous system lymphomas and characterized xenografts from four patients with primary and four secondary central nervous system lymphomas using immunohistochemistry, flow cytometry, and nucleic acid sequencing technology. In reimplantation experiments, we analyzed propagation 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 return to the central nervous system and eye after intrasplenic transplantation, mimicking central nervous system and primary vitreoretinal lymphoma pathology, respectively. Transcriptomic analysis revealed clear signatures for lymphoma cells in the brain compared to the spleen, and a low level of overlap of genes commonly regulated in primary and secondary central nervous system lymphomas. Conclusion: This in vivo tumor model preserves key features of primary and secondary central nervous system lymphoma and can be used to explore critical pathways to the central nervous system and retinal trophism with the aim of finding new targets for new therapeutic approaches.
AB - Objectives: It is still unknown how and why lymphoma cells lodge in the central nervous system and in the vitreoretinal compartment in primary diffuse large B-cell lymphoma of the central nervous system. Our aim was to create an in vivo model to study the tropism of lymphoma cells towards the central nervous system. Methods: We constructed a mouse xenograft model for patients' own central nervous system lymphomas and characterized xenografts from four patients with primary and four secondary central nervous system lymphomas using immunohistochemistry, flow cytometry, and nucleic acid sequencing technology. In reimplantation experiments, we analyzed propagation 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 return to the central nervous system and eye after intrasplenic transplantation, mimicking central nervous system and primary vitreoretinal lymphoma pathology, respectively. Transcriptomic analysis revealed clear signatures for lymphoma cells in the brain compared to the spleen, and a low level of overlap of genes commonly regulated in primary and secondary central nervous system lymphomas. Conclusion: This in vivo tumor model preserves key features of primary and secondary central nervous system lymphoma and can be used to explore critical pathways to the central nervous system and retinal trophism with the aim of finding new targets for new therapeutic approaches.
UR – http://www.scopus.com/inward/record.url?scp=85153770764&partnerID=8YFLogxK
U2 - 10.1111/inch 12899
DO-10.1111/nan.12899
M3 – Newspaper article
C2 - 36879456
AN - SCOPUS:85153770764
VL - 49
JO – Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
SN - 0305-1846
IS - 2
M1 - e12899
AND -
Isbell LK, Tschuch C, Doostkam S, Waldeck S, Andrieux G, Shoumariyeh K et al.Patient-derived xenograft mouse models to study the central nervous system and retinal tropism of primary and secondary central nervous system lymphomas.Neuropathology and Applied Neurobiology. 2023 April;49(2):e12899. doi: 10.1111/nan.12899