| Autor: |
Priya Saikumar Lakshmi, Cliff I Oduor, Catherine S Forconi, Viriato M’Bana, Courtney Bly, Rachel M Gerstein, Juliana A Otieno, John M Ong’echa, Christian Münz, Micah A Luftig, Michael A Brehm, Jeffrey A Bailey, Ann M Moormann |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Life Science Alliance. 6:e202101355 |
| ISSN: |
2575-1077 |
| Popis: |
Endemic Burkitt lymphoma (BL) is a childhood cancer in sub-Saharan Africa characterized by Epstein–Barr virus and malaria-associated aberrant B-cell activation andMYCchromosomal translocation. Survival rates hover at 50% after conventional chemotherapies; therefore, clinically relevant models are necessary to test additional therapies. Hence, we established five patient-derived BL tumor cell lines and corresponding NSG-BL avatar mouse models. Transcriptomics confirmed that our BL lines maintained fidelity from patient tumors to NSG-BL tumors. However, we found significant variation in tumor growth and survival among NSG-BL avatars and in Epstein–Barr virus protein expression patterns. We tested rituximab responsiveness and found one NSG-BL model exhibiting direct sensitivity, characterized by apoptotic gene expression counterbalanced by unfolded protein response and mTOR pro-survival pathways. In rituximab-unresponsive tumors, we observed an IFN-α signature confirmed by the expression of IRF7 and ISG15. Our results demonstrate significant inter-patient tumor variation and heterogeneity, and that contemporary patient-derived BL cell lines and NSG-BL avatars are feasible tools to guide new therapeutic strategies and improve outcomes for these children. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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