PUBLICATION

Leukemic cell xenograft in zebrafish embryo for investigating drug efficacy

Authors
Pruvot, B., Jacquel, A., Droin, N., Auberger, P., Bouscary, D., Tamburini, J., Muller, M., Fontenay, M., Chluba, J., and Solary, E.
ID
ZDB-PUB-110119-29
Date
2011
Source
Haematologica   96(4): 612-616 (Journal)
Registered Authors
Muller, Marc
Keywords
Acute Myeloid Leukemia, Animal model, Pharmacology
MeSH Terms
  • Animals
  • Antineoplastic Agents/pharmacology*
  • Benzamides
  • Cell Line, Tumor/drug effects
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical*
  • Humans
  • Imatinib Mesylate
  • Jurkat Cells
  • K562 Cells
  • Piperazines/pharmacology
  • Pyrimidines/pharmacology
  • Tretinoin/pharmacology
  • Xenograft Model Antitumor Assays*
  • Zebrafish/surgery*
PubMed
21228037 Full text @ Haematologica
Abstract
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 of non-teratogenic drugs.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping