This application is from a collaborative research team which proposes to develop, characterize, and validate mouse models of myeloid leukemia as a component of the National Cancer Institute's Mouse Models of Human Cancer Consortium. The applicant team consists of investigators located at the University of California, San Francisco, St. Jude Children's Research Hospital, the University of Chicago, and the University of Minnesota who are expert in various aspects of mouse model development including targeted mutagenesis, conditional gene expression, adoptive transfer into irradiated recipients, retroviral-mediated mutagenesis, cytogenetic and spectral karyotype analysis, fluorescence in situ hybridization, immunocytochemical staining, and preclinical evaluation of novel therapeutics. The proposed studies will focus on generating new mouse models that reproduce common genetic lesions found in human leukemias, and upon fully characterizing and exploiting both new and existing models. A second aspect of this proposal involves efforts to enhance the technologies that exist for engineering genetic alterations in mice for discovering mutations, and for performing phenotypic and chromosomal analysis of cancer cells. The applicant group will develop an Internet Website to distribute information to the scientific research community and anticipates collaborating to characterize and validate murine models developed by other groups. The applicant team is fully committed to sharing resources and data with other members of the MHCC to achieve the overall goal of developing better murine cancer models and in ultimately translating this research into better therapies for human patients.