Myc-induced T cell leukemia in transgenic zebrafish.
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.
Langenau
David M
DM
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Traver
David
D
Ferrando
Adolfo A
AA
Kutok
Jeffery L
JL
Aster
Jon C
JC
Kanki
John P
JP
Lin
Shuo
S
Prochownik
Ed
E
Trede
Nikolaus S
NS
Zon
Leonard I
LI
Look
A Thomas
AT
D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D016259:Genes, myc; D049452:Green Fluorescent Proteins; D007668:Kidney / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000473:pathology; D017254:Leukemic Infiltration; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation; D009368:Neoplasm Transplantation; D009830:Olfactory Bulb / Q000473:pathology; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D013950:Thymus Gland / Q000473:pathology; D019076:Transgenes; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; C499308:Rag2 protein, mouse; D011993:Recombinant Fusion Proteins; C064655:V(D)J recombination activating protein 2; D049452:Green Fluorescent Proteins