1. Impact of the Injection Site on Growth Characteristics, Phenotype and Sensitivity towards Cytarabine of Twenty Acute Leukaemia Patient-Derived Xenograft Models
- Author
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Milena Pantic, Dorothee Lenhard, Julia Schueler, Anna Edinger, Gabriele Greve, Michael Lübbert, and Eva Oswald
- Subjects
acute leukaemia ,0301 basic medicine ,Cancer Research ,Implantation Site ,Biology ,lcsh:RC254-282 ,Article ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,cytarabine ,Injection site ,medicine ,Overall survival ,Tumor xenograft ,medicine.diagnostic_test ,flow cytometry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Phenotype ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cytarabine ,Cancer research ,patient-derived xenografts ,tumour microenvironment ,Infiltration (medical) ,medicine.drug - Abstract
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.
- Published
- 2020