期刊
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
卷 96, 期 4, 页码 612-616出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2010.031401
关键词
Zebrafish model; acute leukemia; antileukemic drugs; pharmacology; teratogenicity
类别
资金
- Ligue Nationale Contre le Cancer (Labeled group, ES)
- Agence Nationale de la Recherche (LACAM)
- National Institute of Cancer (INCa) [ACM07]
- Fondation pour la Recherche Medicale (Prix Jean et Ana Paneboeuf)
Zebrafish were proposed as an alternative to mammalian models to assess the efficacy and toxicity of anti-leukemic 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 anti-leukemic activity in such models. Altogether, xenografted leukemic cells in zebrafish embryos are a pharmacologically relevant model for screening non-teratogenic drugs.
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