Preclinical modeling of cytosine arabinoside response in Mll-Enl translocator mouse leukemias.
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.
Cano
Florencia
F
Leeds Institute of Molecular Medicine, Section of Experimental Therapeutics, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK.
Pannel
Richard
R
Follows
George A
GA
Rabbitts
Terence H
TH
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*
D000970:Antineoplastic Agents; C472772:MLL-ELL fusion protein, human; D015514:Oncogene Proteins, Fusion; D003561:Cytarabine; D051788:Myeloid-Lymphoid Leukemia Protein