Abstract
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.
| Original language | English |
|---|---|
| Article number | e12899 |
| Journal | Neuropathology and Applied Neurobiology |
| Volume | 49 |
| Issue number | 2 |
| Pages (from-to) | e12899 |
| ISSN | 0305-1846 |
| DOIs | |
| Publication status | Published - 04.2023 |
Funding
Nikolas von Bubnoff receives funding from the Deutsche Forschungsgemeinschaft (DFG) (Project ID: 386260575) and the German Federal Ministry of Education and Research (BMBF) within the OUTLIVE consortium (Project ID: 01KD2103A). Melanie Boerries is supported by the Deutsche Forschungsgemeinschaft (DFG) – CRC 850 subprojects C9 and Z1, CRC1479 (Project ID: 441891347‐S1), CRC 1160 (Project ID 256073931‐Z02), CRC1453 (Project ID 431984000 – S1) and TRR167 (Project Z01). We also acknowledge funding from the German Federal Ministry of Education and Research (BMBF) within the Medical Informatics Funding Scheme – MIRACUM‐FKZ 01ZZ1801B (M.B.) and EkoEstMed–FKZ 01ZZ2015 (G.A.). We thank Dieter Herchenbach and Jan Bodinek‐Wersing for cell sorting and Dietmar Pfeifer for sequencing. We thank Jonathan R Isbell and Juergen Lohmeyer for proofreading. Open Access funding enabled and organized by Projekt DEAL. Nikolas von Bubnoff received research support from Novartis and honoraria from Novartis, Takeda and the Forum für Medizinische Fortbildung. Khalid Shoumariyeh received honoraria from Novartis, Blueprint Medicines and Pfizer. Peter C Reinacher receives research support from Else Kröner‐Fresenius Foundation (Germany) and Fraunhofer Foundation (Germany), received personal honoraria for lectures or advice from Boston Scientific (USA) and Brainlab (Germany) and is a consultant for Boston Scientific (USA), Inomed (Germany) and Brainlab (Germany). The other authors have no competing interests to declare that are relevant to the content of this article.
Research Areas and Centers
- Research Area: Luebeck Integrated Oncology Network (LION)
- Centers: University Cancer Center Schleswig-Holstein (UCCSH)
DFG Research Classification Scheme
- 2.22-14 Hematology, Oncology
- 2.21-05 Immunology
