Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 27 April 2007:
Vol. 316. no. 5824, pp. 600 - 604
DOI: 10.1126/science.1139851
Prev | Table of Contents | Next

Reports

Modeling the Initiation and Progression of Human Acute Leukemia in Mice

Frédéric Barabé,1,2,3,4* James A. Kennedy,1,5* Kristin J. Hope,1,5 John E. Dick1,5{dagger}

Our understanding of leukemia development and progression has been hampered by the lack of in vivo models in which disease is initiated from primary human hematopoietic cells. We showed that upon transplantation into immunodeficient mice, primitive human hematopoietic cells expressing a mixed-lineage leukemia (MLL) fusion gene generated myeloid or lymphoid acute leukemias, with features that recapitulated human diseases. Analysis of serially transplanted mice revealed that the disease is sustained by leukemia-initiating cells (L-ICs) that have evolved over time from a primitive cell type with a germline immunoglobulin heavy chain (IgH) gene configuration to a cell type containing rearranged IgH genes. The L-ICs retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. The properties of these cells provide a biological basis for several clinical hallmarks of MLL leukemias.

1 Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario, M5G 1L7, Canada.
2 Department of Medicine, Laval University, Québec, G1K 7P4, Canada.
3 Department of Hematology, Enfant-Jesus Hospital, Qué-bec, G1J 1Z4, Canada.
4 Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Québec–Centre Hospitalier de l'Université Laval, Québec, G1V 4G2, Canada.
5 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: jdick{at}uhnres.utoronto.ca

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Identification of tumor-initiating cells in a highly aggressive brain tumor using promoter activity of nucleostemin.
A. Tamase, T. Muraguchi, K. Naka, S. Tanaka, M. Kinoshita, T. Hoshii, M. Ohmura, H. Shugo, T. Ooshio, M. Nakada, et al. (2009)
PNAS 106, 17163-17168
   Abstract »    Full Text »    PDF »
Chelation of intracellular iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and myeloma cells.
Y. Eberhard, S. P. McDermott, X. Wang, M. Gronda, A. Venugopal, T. E. Wood, R. Hurren, A. Datti, R. A. Batey, J. Wrana, et al. (2009)
Blood 114, 3064-3073
   Abstract »    Full Text »    PDF »
The leukemic stem cell niche: current concepts and therapeutic opportunities.
S. W. Lane, D. T. Scadden, and D. G. Gilliland (2009)
Blood 114, 1150-1157
   Abstract »    Full Text »    PDF »
Acute myeloid leukemia induced by MLL-ENL is cured by oncogene ablation despite acquisition of complex genetic abnormalities.
S. J. Horton, V. Walf-Vorderwulbecke, S. J. Chatters, N. J. Sebire, J. de Boer, and O. Williams (2009)
Blood 113, 4922-4929
   Abstract »    Full Text »    PDF »
Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia.
M. G. Guenther, L. N. Lawton, T. Rozovskaia, G. M. Frampton, S. S. Levine, T. L. Volkert, C. M. Croce, T. Nakamura, E. Canaani, and R. A. Young (2008)
Genes & Dev. 22, 3403-3408
   Abstract »    Full Text »    PDF »
Stem cell concepts renew cancer research.
J. E. Dick (2008)
Blood 112, 4793-4807
   Abstract »    Full Text »    PDF »
Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells.
D. C. Taussig, F. Miraki-Moud, F. Anjos-Afonso, D. J. Pearce, K. Allen, C. Ridler, D. Lillington, H. Oakervee, J. Cavenagh, S. G. Agrawal, et al. (2008)
Blood 112, 568-575
   Abstract »    Full Text »    PDF »
The Treatment of Adults with Acute Lymphoblastic Leukemia.
A. Fielding (2008)
Hematology 2008, 381-389
   Abstract »    Full Text »    PDF »
Comment on "Tumor Growth Need Not Be Driven by Rare Cancer Stem Cells".
J. A. Kennedy, F. Barabe, A. G. Poeppl, J. C. Y. Wang, and J. E. Dick (2007)
Science 318, 1722c
   Abstract »    Full Text »    PDF »
Implication of the Molecular Characterization of Acute Myeloid Leukemia.
H. Dohner (2007)
Hematology 2007, 412-419
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)