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Research Articles: Therapeutics, Targets, and Development

Preclinical modeling of cytosine arabinoside response in Mll-Enl translocator mouse leukemias

¹ MRC Laboratory of Molecular Biology; ² Addenbrooke's Hospital, Cambridge, United Kingdom and ³ Leeds Institute of Molecular Medicine, Leeds, United Kingdom

Requests for reprints: Terence H. Rabbitts, Leeds Institute of Molecular Medicine, Section of Experimental Therapeutics, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds, LS9 7TF, United Kingdom. Phone: 44-113-343-8518; Fax: 44-113-343-8601. E-mail: thr{at}leeds.ac.uk

Abstract

Mouse models of human cancer are a potential preclinical setting for drug testing and for development of methods for delivery of macromolecular drugs to tumors. We have assessed a mouse model of leukemia caused by Mll-Enl protein fusion as a preclinical situation in which myeloid-lineage leukemia results from de novo occurrence of chromosomal translocations between Mll and Enl genes. Here, we show that the mouse leukemias respond to cytosine arabinoside, a frontline treatment for human leukemia. The observations show that the myeloid cells are susceptible to the drug and the mice undergo a remission that comprises a reduction of the myeloid population of cells and recovery of the lymphoid population. This translocator model should therefore prove useful for future drug assessments against the recurrent mixed-lineage leukemia–associated translocations. [Mol Cancer Ther 2008;7(3):730–5]

Grant support: Medical Research Council; César Milstein Memorial Studentship of the Darwin Trust, Edinburgh (F. Cano).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: Current address for F. Cano: Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, United Kingdom.

⁴ Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

⁵ R. Pannel and T.H. Rabitts, unpublished data.

Received 9/ 4/07; revised 11/ 5/07; accepted 12/11/07.