Retroviral transduction models of Ph+ leukemia: Advantages and limitationsfor modeling human hematological malignancies in mice

There are two commonly used approaches to modeling human leukemia in mice: generation of mutant mice by traditional transgenic or knock-out/knock-in m ethods and retroviral bone marrow transduction and transplantation. For mod eling leukemia, the retroviral model system has some distinct advantages ov er transgenic mice. Testing different forms and mutants of a given oncogene is much easier with the retroviral system and avoids the potential deleter ious effects of expression of a transgene in nonhematopoietic tissues and d uring development. The retroviral provirus serves as a clonal marker of a t ransduced cell, facilitating analysis of clonality and transplantability of the malignancy. Finally, the retroviral system allows the assessment of th e action of an oncogene in different subsets of hematopoietic precursor cel ls in the bone marrow, which is difficult or impossible with transgenic mod els. This article summarizes recent progress in modeling human Philadelphia -positive leukemia in mice with the retroviral bone marrow transduction/tra nsplantation system and emphasizes the advantages and limitations of this a pproach with examples from the BCR-ABL leukemogenesis literature. (C) 2001 Academic Press.