title: Leukemic cell xenograft in zebrafish embryo for investigating drug efficacy.
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.
authors.affiliation: Inserm UMR866, Faculty of Medicine, Dijon, France. eric.solary@igr.fr
authors.forename: Benoist
authors.initials: B
authors.lastname: Pruvot
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jacquel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Droin
authors.forename: Patrick
authors.initials: P
authors.lastname: Auberger
authors.forename: Didier
authors.initials: D
authors.lastname: Bouscary
authors.forename: Jérome
authors.initials: J
authors.lastname: Tamburini
authors.forename: Marc
authors.initials: M
authors.lastname: Muller
authors.forename: Michaela
authors.initials: M
authors.lastname: Fontenay
authors.forename: Johanna
authors.initials: J
authors.lastname: Chluba
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D045744:Cell Line, Tumor / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000068877:Imatinib Mesylate; D019169:Jurkat Cells; D020014:K562 Cells; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish / Q000601:surgery*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014212:Tretinoin; D000068877:Imatinib Mesylate