Leukaemia xenotransplantation in zebrafish - chemotherapy response assay in vivo

Corkery, D.P., Dellaire, G., and Berman, J.N.
British journal of haematology   153(6): 786-789 (Journal)
Registered Authors
Berman, Jason, Corkery, Dale
zebrafish, myeloid leukaemia, chemotherapy, chemical screening, xenotransplantation
MeSH Terms
  • Animals
  • Antineoplastic Agents/therapeutic use*
  • Cell Proliferation/drug effects
  • Humans
  • Leukemia/drug therapy*
  • Xenograft Model Antitumor Assays/methods*
  • Zebrafish
21517816 Full text @ Br. J. Haematol.
As the molecular understanding of cancer pathogenesis has evolved, so has the need for innovative assays to identify novel targeted therapeutic agents. Characterization of specific tumour-drug interactions would enable the design of more personalized treatment with improved outcomes and reduced toxicity. The zebrafish has emerged as a robust animal model of human malignancy due to conserved genetics and cell biology (Amatruda & Patton, 2008; Payne & Look, 2009). Xenotransplantation of human cancer cells into zebrafish was initiated in 2005 using a melanoma xenograft (Lee et al, 2005). Subsequent studies determined that incubation at 35°C enabled normal growth of injected human cell lines without compromising zebrafish embryogenesis and established the yolk sac and 48 h post-fertilization (hpf) as the ideal anatomic location and developmental stage for injection (Haldi et al, 2006). At this stage, adaptive immune responses are not yet established in the embryo, permitting injection of human cells without requiring immunosuppression (Lam et al, 2004; Haldi et al, 2006; Nicoli et al, 2007). Proliferation of xenografted melanoma cells was documented using a haemocytometer (Haldi et al, 2006); while proliferation of xenografted leukaemia cells was determined by fluorescence and embryo demise (Pruvot et al, 2011). These reports provided a critical foundation, however further refinement and proof-of-principle studies are necessary for this approach to be practically applied to cancer drug discovery and clinically employed for therapeutic drug responses. To this end, we transplanted K562 and NB-4 human leukaemia cell lines into casper embryos, a zebrafish combinatorial pigment mutant (White et al, 2008), and developed a robust cell proliferation assay demonstrating in vivo targeted therapeutic inhibition of these leukaemias.
Genes / Markers
Show all Figures
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes