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Open AccessArticle

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

1
Charles River Discovery Research Services Germany GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany
2
Department of Medicine I, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1349; https://doi.org/10.3390/cancers12051349
Received: 28 April 2020 / Revised: 22 May 2020 / Accepted: 23 May 2020 / Published: 25 May 2020
(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)
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. View Full-Text
Keywords: patient-derived xenografts; acute leukaemia; tumour microenvironment; flow cytometry; cytarabine patient-derived xenografts; acute leukaemia; tumour microenvironment; flow cytometry; cytarabine
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Schueler, J.; Greve, G.; Lenhard, D.; Pantic, M.; Edinger, A.; Oswald, E.; Luebbert, M. Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models. Cancers 2020, 12, 1349.

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