Journal ArticleDOI
Myc-induced T cell leukemia in transgenic zebrafish.
David M. Langenau,David Traver,Adolfo A. Ferrando,Jeffery L. Kutok,Jon C. Aster,John P. Kanki,Shuo Lin,Edward V. Prochownik,Nikolaus S. Trede,Leonard I. Zon,A. Thomas Look +10 more
TLDR
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.Abstract:
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.read more
Citations
More filters
Journal ArticleDOI
Animal models of human disease: zebrafish swim into view.
TL;DR: This Review surveys the achievements and potential of zebrafish for modelling human diseases and for drug discovery and development.
Journal ArticleDOI
Acute lymphoblastic leukaemia
TL;DR: Advances in understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease.
Journal ArticleDOI
In vivo drug discovery in the zebrafish
TL;DR: By combining the scale and throughput of in vitro screens with the physiological complexity of animal studies, the zebrafish promises to contribute to several aspects of the drug development process, including target identification, disease modelling, lead discovery and toxicology.
Journal ArticleDOI
c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma
Andrew P. Weng,John M. Millholland,Yumi Yashiro-Ohtani,Marie Laure Arcangeli,Arthur Lau,Carol Wai,Cristina Del Bianco,Carlos G. Rodriguez,Hong Sai,John W. Tobias,Yue-Ming Li,Michael S. Wolfe,Cathy Shachaf,Dean W. Felsher,Stephen C. Blacklow,Warren S. Pear,Jon C. Aster +16 more
TL;DR: In this article, the authors identified c-myc as a direct target of Notch1 in Notch-dependent T-ALL cell lines, in which Notch accounts for the majority of cmyc expression.
Journal ArticleDOI
Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants
TL;DR: The zebrafish is firmly established as a genetic model for the study of vertebrate blood development and its blood-forming system is characterized to provide a cellular context in which to study the genetics of hematopoiesis.
References
More filters
Journal ArticleDOI
The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio
P. Haffter,Michael Granato,Michael Brand,Mary C. Mullins,M. Hammerschmidt,D. A. Kane,J. Odenthal,F. J. M. Van Eeden,Y.-J. Jiang,Carl-Philipp Heisenberg,Robert N. Kelsh,Makoto Furutani-Seiki,Elisabeth Vogelsang,D. Beuchle,U. Schach,C. Fabian,Christiane Nüsslein-Volhard +16 more
TL;DR: It is estimated that the 372 genes defined by the mutants probably represent more than half of all genes that could have been discovered using the criteria of the screen, and the limits and the potentials of a genetic saturation screen in the zebrafish.
Journal ArticleDOI
A genetic screen for mutations affecting embryogenesis in zebrafish
Wolfgang Driever,Lilianna Solnica-Krezel,Alexander F. Schier,Stephan C.F. Neuhauss,Jarema Malicki,Derek L. Stemple,Didier Y.R. Stainier,Fried J. T. Zwartkruis,Salim Abdelilah,Zehava Rangini,J Belak,C Boggs +11 more
TL;DR: The results from the first application of such a large-scale genetic screening to vertebrate development of mutagenized zebrafish demonstrate that mutations affecting a variety of developmental processes can be efficiently recovered from zebra fish.
Journal ArticleDOI
c-MYC: more than just a matter of life and death.
TL;DR: Regulatable transgenic mouse models of oncogenesis have shed light on the role of c-MYC in tumour progression and provide hope for effective cancer therapies.
Journal ArticleDOI
Suppression of Myc-Induced Apoptosis in β Cells Exposes Multiple Oncogenic Properties of Myc and Triggers Carcinogenic Progression
TL;DR: The data indicate that highly complex neoplastic lesions can be both induced and maintained in vivo by a simple combination of two interlocking molecular lesions.
Journal ArticleDOI
Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC
Meenakshi Jain,Constadina Arvanitis,Kenneth Chu,William C. Dewey,Edith A. Leonhardt,Maxine Trinh,Christopher D. Sundberg,J. Michael Bishop,Dean W. Felsher +8 more
TL;DR: It is demonstrated that brief inactivation of MYC results in the sustained regression of tumors and the differentiation of osteogenic sarcoma cells into mature osteocytes, raising the possibility that transient in activation ofMYC may be an effective therapy for certain cancers.
Related Papers (5)
BRAF Mutations Are Sufficient to Promote Nevi Formation and Cooperate with p53 in the Genesis of Melanoma
E. Elizabeth Patton,Hans R. Widlund,Jeffery L. Kutok,Kamden R. Kopani,Kamden R. Kopani,James F. Amatruda,James F. Amatruda,Ryan D. Murphey,Ryan D. Murphey,Stephane Berghmans,Elizabeth A. Mayhall,Elizabeth A. Mayhall,David Traver,David Traver,Christopher D.M. Fletcher,Jon C. Aster,Scott R. Granter,A. Thomas Look,Charles Lee,David E. Fisher,Leonard I. Zon,Leonard I. Zon +21 more