Langenau, D.M., Traver, D., Ferrando, A.A., Kutok, J.L., Aster, J.C., Kanki, J.P., Lin, S., Prochownik, E., Trede, N.S., Zon, L.I., and Look, A.T. (2003) Myc-induced T cell leukemia in transgenic zebrafish. Science (New York, N.Y.). 299(5608):887-890.
The zebrafish is an attractive model organism for studying cancer development because of its genetic accessibility. Here we describe the induction of clonally derived T cell acute lymphoblastic leukemia in transgenic zebrafish expressing mouse c-myc under control of the zebrafish Rag2 promoter. Visualization of leukemic cells expressing a chimeric transgene encoding Myc fused to green fluorescent protein (GFP) revealed that leukemias arose in the thymus, spread locally into gill arches and retro-orbital soft tissue, and then disseminated into skeletal muscle and abdominal organs. Leukemic cells homed back to the thymus in irradiated fish transplanted with GFP-labeled leukemic lymphoblasts. This transgenic model provides a platform for drug screens and for genetic screens aimed at identifying mutations that suppress or enhance c-myc- induced carcinogenesis.