van der Weyden, L., Giotopoulos, G., Rust, A. G., Matheson, L. S., van Delft, F. W., Kong, J., Corcoran, A. E., Greaves, M. F., Mullighan, C. G., Huntly, B. J., Adams, D. J. (2011) Modeling the evolution of ETV6-RUNX1-induced B-cell precursor acute lymphoblastic leukemia in mice. BLOOD, 118 (4). pp. 1041-1051. ISSN 0006-4971

Full text not available from this repository.

Abstract

The t(12; 21) translocation that generates the ETV6-RUNX1 (TEL-AML1) fusion gene, is the most common chromosomal rearrangement in childhood cancer and is exclusively associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The translocation arises in utero and is necessary but insufficient for the development of leukemia. Single-nucleotide polymorphism array analysis of ETV6-RUNX1 patient samples has identified multiple additional genetic alterations; however, the role of these lesions in leukemogenesis remains undetermined. Moreover, murine models of ETV6-RUNX1 ALL that faithfully recapitulate the human disease are lacking. To identify novel genes that cooperate with ETV6-RUNX1 in leukemogenesis, we generated a mouse model that uses the endogenous Etv6 locus to coexpress the Etv6-RUNX1 fusion and Sleeping Beauty transposase. An insertional mutagenesis screen was performed by intercrossing these mice with those carrying a Sleeping Beauty transposon array. In contrast to previous models, a substantial proportion (20%) of the offspring developed BCP-ALL. Isolation of the transposon insertion sites identified genes known to be associated with BCP-ALL, including Ebf1 and Epor, in addition to other novel candidates. This is the first mouse model of ETV6RUNX1 to develop BCP-ALL and provides important insight into the cooperating genetic alterations in ETV6-RUNX1 leukemia. (Blood. 2011; 118(4):1041-1051)

Item Type:	Article
Authors (ICR Faculty only):	Greaves, Mel
All Authors:	van der Weyden, L., Giotopoulos, G., Rust, A. G., Matheson, L. S., van Delft, F. W., Kong, J., Corcoran, A. E., Greaves, M. F., Mullighan, C. G., Huntly, B. J., Adams, D. J.
Additional Information:	ISI Document Delivery No.: 798PC Times Cited: 0 Cited Reference Count: 52 van der Weyden, Louise Giotopoulos, George Rust, Alistair G. Matheson, Louise S. van Delft, Frederik W. Kong, Jun Corcoran, Anne E. Greaves, Mel F. Mullighan, Charles G. Huntly, Brian J. Adams, David J. Kay Kendall Leukaemia Fund; Cancer Research-UK; Wellcome Trust; Medical Research Council-UK; Leukaemia & Lymphoma Research UK; Biotechnology and Biological Sciences Research Council; American Lebanese Syrian Associated Charities of St Jude Children's Research Hospital L.v.d.W. is supported by a Fellowship from the Kay Kendall Leukaemia Fund. D.J.A. is supported by Cancer Research-UK and the Wellcome Trust. B.J.H. and G. G. are supported by an Medical Research Council-UK Senior Fellowship (B.J.H.) and Cancer Research-UK. F. W. v. D. and M. F. G. are supported by the Kay Kendall Leukaemia Fund and Leukaemia & Lymphoma Research UK. A. E. C. and L. S. M. are supported by the Biotechnology and Biological Sciences Research Council. C. G. M. is supported by the American Lebanese Syrian Associated Charities of St Jude Children's Research Hospital, and is a Pew Scholar in the Biomedical Sciences. Amer soc hematology Washington
Uncontrolled Keywords:	acute myeloid-leukemia chromosomal translocations tel-aml1 translocation lymphocytic-leukemia bethesda proposals childhood leukemia expression classification identification t(12/21)
Research teams:	ICR divisions > Molecular Pathology > Biology of Childhood Leukaemia
Depositing User:	Alexander Smithson
Date Deposited:	15 Aug 2011 15:27
Last Modified:	15 Aug 2011 15:27
URI:	http://publications.icr.ac.uk/id/eprint/10934

Actions (login required)

View Item