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Leukemic cell xenograft in zebrafish embryo for investigating drug efficacy

By Benoist Pruvot, Arnaud Jacquel, Nathalie Droin, Patrick Auberger, Didier Bouscary, Jérome Tamburini, Marc Muller, Michaela Fontenay, Johanna Chluba and Eric Solary

Abstract

Zebrafish were proposed as an alternative to mammalian models to assess the efficacy and toxicity of antileukemic drugs. Due to the limited number of transgenic zebrafish leukemia models, we explored human leukemic cell xenograft in zebrafish embryos. Human leukemic cell lines and blast cells sorted from patients with acute myelogenous leukemia were injected 48 hours post-fertilization and remained in the circulation of zebrafish embryos for several days without affecting their development. Imatinib and oxaphorines did not demonstrate any toxicity on normal zebrafish embryos and decreased the leukemic burden in animals xenografted with sensitive leukemic cell lines. Two other molecules, all-trans retinoic acid and the translation inhibitor 4EGI-1, demonstrated teratogenic effects at concentrations shown to be efficient in vitro, which precluded investigation of their antileukemic activity in such models. Altogether, xenografted leukemic cells in zebrafish embryos are a pharmacologically relevant model for screening non-teratogenic drugs

Topics: Brief Report
Publisher: Ferrata Storti Foundation
OAI identifier: oai:pubmedcentral.nih.gov:3069240
Provided by: PubMed Central
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