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Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models

Rodent models have contributed significantly to the understanding of haematological malignancies. One important model system in this context are patient-derived xenografts (PDX). In the current study, we examined 20 acute leukaemia PDX models for growth behaviour, infiltration in haemopoietic organs...

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Autores principales: Schueler, Julia, Greve, Gabriele, Lenhard, Dorothée, Pantic, Milena, Edinger, Anna, Oswald, Eva, Luebbert, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281503/
https://www.ncbi.nlm.nih.gov/pubmed/32466316
http://dx.doi.org/10.3390/cancers12051349
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author Schueler, Julia
Greve, Gabriele
Lenhard, Dorothée
Pantic, Milena
Edinger, Anna
Oswald, Eva
Luebbert, Michael
author_facet Schueler, Julia
Greve, Gabriele
Lenhard, Dorothée
Pantic, Milena
Edinger, Anna
Oswald, Eva
Luebbert, Michael
author_sort Schueler, Julia
collection PubMed
description Rodent models have contributed significantly to the understanding of haematological malignancies. One important model system in this context are patient-derived xenografts (PDX). In the current study, we examined 20 acute leukaemia PDX models for growth behaviour, infiltration in haemopoietic organs and sensitivity towards cytarabine. PDX were injected intratibially (i.t.), intrasplenicaly (i.s.) or subcutaneously (s.c.) into immune compromised mice. For 18/20 models the engraftment capacity was independent of the implantation site. Two models could exclusively be propagated in one or two specific settings. The implantation site did influence tumour growth kinetics as median overall survival differed within one model depending on the injection route. The infiltration pattern was similar in i.t. and i.s. models. In contrast to the s.c. implantation, only one model displayed circulating leukaemic cells outside of the locally growing tumour mass. Cytarabine was active in all four tested models. Nevertheless, the degree of sensitivity was specific for an individual model and implantation site. In summary, all three application routes turned out to be feasible for the propagation of PDX. Nevertheless, the distinct differences between the settings highlight the need for well characterized platforms to ensure the meaningful interpretation of data generated using those powerful tools.
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spelling pubmed-72815032020-06-17 Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models Schueler, Julia Greve, Gabriele Lenhard, Dorothée Pantic, Milena Edinger, Anna Oswald, Eva Luebbert, Michael Cancers (Basel) Article Rodent models have contributed significantly to the understanding of haematological malignancies. One important model system in this context are patient-derived xenografts (PDX). In the current study, we examined 20 acute leukaemia PDX models for growth behaviour, infiltration in haemopoietic organs and sensitivity towards cytarabine. PDX were injected intratibially (i.t.), intrasplenicaly (i.s.) or subcutaneously (s.c.) into immune compromised mice. For 18/20 models the engraftment capacity was independent of the implantation site. Two models could exclusively be propagated in one or two specific settings. The implantation site did influence tumour growth kinetics as median overall survival differed within one model depending on the injection route. The infiltration pattern was similar in i.t. and i.s. models. In contrast to the s.c. implantation, only one model displayed circulating leukaemic cells outside of the locally growing tumour mass. Cytarabine was active in all four tested models. Nevertheless, the degree of sensitivity was specific for an individual model and implantation site. In summary, all three application routes turned out to be feasible for the propagation of PDX. Nevertheless, the distinct differences between the settings highlight the need for well characterized platforms to ensure the meaningful interpretation of data generated using those powerful tools. MDPI 2020-05-25 /pmc/articles/PMC7281503/ /pubmed/32466316 http://dx.doi.org/10.3390/cancers12051349 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schueler, Julia
Greve, Gabriele
Lenhard, Dorothée
Pantic, Milena
Edinger, Anna
Oswald, Eva
Luebbert, Michael
Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models
title Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models
title_full Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models
title_fullStr Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models
title_full_unstemmed Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models
title_short Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models
title_sort impact of the injection site on growth characteristics, phenotype and sensitivity towards cytarabine of twenty acute leukaemia patient-derived xenograft models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281503/
https://www.ncbi.nlm.nih.gov/pubmed/32466316
http://dx.doi.org/10.3390/cancers12051349
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