ReviewUsing zebrafish models of leukemia to streamline drug screening and discovery

- Targeted leukemia therapies have been limited due to unexpected off-target effects.
- Phenotype-based screening provides an unbiased means of novel drug discovery.
- The zebrafish is amenable to genetic and xenograft leukemia models.
- Zebrafish leukemia models provide a unique platform for phenotype-based drug screens.

Current treatment strategies for acute leukemias largely rely on nonspecific cytotoxic drugs that result in high therapy-related morbidity and mortality. Cost-effective, pertinent animal models are needed to link in vitro studies with the development of new therapeutic agents in clinical trials on a high-throughput scale. However, targeted therapies have had limited success moving from bench to clinic, often due to unexpected off-target effects. The zebrafish has emerged as a reliable in vivo tool for modeling human leukemia. Zebrafish genetic and xenograft models of acute leukemia provide an unprecedented opportunity to conduct rapid, phenotype-based screens. This allows for the identification of relevant therapies while simultaneously evaluating drug toxicity, thus circumventing the limitations of target-centric approaches.