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A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia
Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML us...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382660/ https://www.ncbi.nlm.nih.gov/pubmed/25794133 http://dx.doi.org/10.1038/bcj.2015.19 |
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author | Saland, E Boutzen, H Castellano, R Pouyet, L Griessinger, E Larrue, C de Toni, F Scotland, S David, M Danet-Desnoyers, G Vergez, F Barreira, Y Collette, Y Récher, C Sarry, J-E |
author_facet | Saland, E Boutzen, H Castellano, R Pouyet, L Griessinger, E Larrue, C de Toni, F Scotland, S David, M Danet-Desnoyers, G Vergez, F Barreira, Y Collette, Y Récher, C Sarry, J-E |
author_sort | Saland, E |
collection | PubMed |
description | Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγ(c)(null) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies. |
format | Online Article Text |
id | pubmed-4382660 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43826602015-04-07 A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia Saland, E Boutzen, H Castellano, R Pouyet, L Griessinger, E Larrue, C de Toni, F Scotland, S David, M Danet-Desnoyers, G Vergez, F Barreira, Y Collette, Y Récher, C Sarry, J-E Blood Cancer J Original Article Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγ(c)(null) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies. Nature Publishing Group 2015-03 2015-03-20 /pmc/articles/PMC4382660/ /pubmed/25794133 http://dx.doi.org/10.1038/bcj.2015.19 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Saland, E Boutzen, H Castellano, R Pouyet, L Griessinger, E Larrue, C de Toni, F Scotland, S David, M Danet-Desnoyers, G Vergez, F Barreira, Y Collette, Y Récher, C Sarry, J-E A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia |
title | A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia |
title_full | A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia |
title_fullStr | A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia |
title_full_unstemmed | A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia |
title_short | A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia |
title_sort | robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382660/ https://www.ncbi.nlm.nih.gov/pubmed/25794133 http://dx.doi.org/10.1038/bcj.2015.19 |
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