Myc-induced T cell leukemia in transgenic zebrafish

被引:412
作者
Langenau, DM
Traver, D
Ferrando, AA
Kutok, JL
Aster, JC
Kanki, JP
Lin, S
Prochownik, E
Trede, NS
Zon, LI
Look, AT
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[2] Childrens Hosp Pittsburgh, Div Hematol Oncol, Pittsburgh, PA 15213 USA
[3] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
[4] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA
关键词
D O I
10.1126/science.1080280
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:887 / 890
页数:4
相关论文
共 24 条
[1]   Transgenic models of lymphoid neoplasia and development of a pan-hematopoietic vector [J].
Adams, JM ;
Harris, AW ;
Strasser, A ;
Ogilvy, S ;
Cory, S .
ONCOGENE, 1999, 18 (38) :5268-5277
[2]   Zebrafish as a cancer model system [J].
Amatruda, JF ;
Shepard, JL ;
Stern, HM ;
Zon, LI .
CANCER CELL, 2002, 1 (03) :229-231
[3]   Ethylnitrosourea induces neoplasia in zebrafish (Danio rerio) [J].
Beckwith, LG ;
Moore, JL ;
Tsao-Wu, GS ;
Harshbarger, JC ;
Cheng, KC .
LABORATORY INVESTIGATION, 2000, 80 (03) :379-385
[4]   Myelopoiesis in the zebrafish, Danio rerio [J].
Bennett, CM ;
Kanki, JP ;
Rhodes, J ;
Liu, TX ;
Paw, BH ;
Kieran, MW ;
Langenau, DM ;
Delahaye-Brown, A ;
Zon, LI ;
Fleming, MD ;
Look, AT .
BLOOD, 2001, 98 (03) :643-651
[5]  
Driever W, 1996, DEVELOPMENT, V123, P37
[6]  
Haffter P, 1996, DEVELOPMENT, V123, P1
[7]   Characterization of three isotypes of immunoglobulin light chains and T-cell antigen receptor α in zebrafish [J].
Haire, RN ;
Rast, JP ;
Litman, RT ;
Litman, GW .
IMMUNOGENETICS, 2000, 51 (11) :915-923
[8]   Zebrafish myelopoiesis and blood cell development [J].
Hsu, K ;
Kanki, JP ;
Look, AT .
CURRENT OPINION IN HEMATOLOGY, 2001, 8 (04) :245-251
[9]   Sustained loss of a neoplastic phenotype by brief inactivation of MYC [J].
Jain, M ;
Arvanitis, C ;
Chu, K ;
Dewey, W ;
Leonhardt, E ;
Trinh, M ;
Sundberg, CD ;
Bishop, JM ;
Felsher, DW .
SCIENCE, 2002, 297 (5578) :102-104
[10]   Artificial chromosome transgenesis reveals long-distance negative regulation of rag1 in zebrafish [J].
Jessen, JR ;
Willett, CE ;
Lin, S .
NATURE GENETICS, 1999, 23 (01) :15-16