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Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies
Endemic Burkitt lymphoma (BL) is a childhood cancer in sub-Saharan Africa characterized by Epstein–Barr virus and malaria-associated aberrant B-cell activation and MYC chromosomal translocation. Survival rates hover at 50% after conventional chemotherapies; therefore, clinically relevant models are...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990458/ https://www.ncbi.nlm.nih.gov/pubmed/36878637 http://dx.doi.org/10.26508/lsa.202101355 |
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author | Saikumar Lakshmi, Priya Oduor, Cliff I Forconi, Catherine S M’Bana, Viriato Bly, Courtney Gerstein, Rachel M Otieno, Juliana A Ong’echa, John M Münz, Christian Luftig, Micah A Brehm, Michael A Bailey, Jeffrey A Moormann, Ann M |
author_facet | Saikumar Lakshmi, Priya Oduor, Cliff I Forconi, Catherine S M’Bana, Viriato Bly, Courtney Gerstein, Rachel M Otieno, Juliana A Ong’echa, John M Münz, Christian Luftig, Micah A Brehm, Michael A Bailey, Jeffrey A Moormann, Ann M |
author_sort | Saikumar Lakshmi, Priya |
collection | PubMed |
description | Endemic Burkitt lymphoma (BL) is a childhood cancer in sub-Saharan Africa characterized by Epstein–Barr virus and malaria-associated aberrant B-cell activation and MYC chromosomal 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. |
format | Online Article Text |
id | pubmed-9990458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-99904582023-03-08 Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies Saikumar Lakshmi, Priya Oduor, Cliff I Forconi, Catherine S M’Bana, Viriato Bly, Courtney Gerstein, Rachel M Otieno, Juliana A Ong’echa, John M Münz, Christian Luftig, Micah A Brehm, Michael A Bailey, Jeffrey A Moormann, Ann M Life Sci Alliance Research Articles Endemic Burkitt lymphoma (BL) is a childhood cancer in sub-Saharan Africa characterized by Epstein–Barr virus and malaria-associated aberrant B-cell activation and MYC chromosomal 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. Life Science Alliance LLC 2023-03-06 /pmc/articles/PMC9990458/ /pubmed/36878637 http://dx.doi.org/10.26508/lsa.202101355 Text en © 2023 Saikumar Lakshmi et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Saikumar Lakshmi, Priya Oduor, Cliff I Forconi, Catherine S M’Bana, Viriato Bly, Courtney Gerstein, Rachel M Otieno, Juliana A Ong’echa, John M Münz, Christian Luftig, Micah A Brehm, Michael A Bailey, Jeffrey A Moormann, Ann M Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies |
title | Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies |
title_full | Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies |
title_fullStr | Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies |
title_full_unstemmed | Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies |
title_short | Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies |
title_sort | endemic burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990458/ https://www.ncbi.nlm.nih.gov/pubmed/36878637 http://dx.doi.org/10.26508/lsa.202101355 |
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