title: Preclinical modeling of cytosine arabinoside response in Mll-Enl translocator mouse leukemias.
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.
authors.affiliation: Leeds Institute of Molecular Medicine, Section of Experimental Therapeutics, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK.
authors.forename: Florencia
authors.initials: F
authors.lastname: Cano
authors.forename: Richard
authors.initials: R
authors.lastname: Pannel
authors.forename: George A
authors.initials: GA
authors.lastname: Follows
authors.forename: Terence H
authors.initials: TH
authors.lastname: Rabbitts
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008962:Models, Theoretical; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C472772:MLL-ELL fusion protein, human; D015514:Oncogene Proteins, Fusion; D003561:Cytarabine; D051788:Myeloid-Lymphoid Leukemia Protein