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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2023
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.
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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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