Modeling myeloid leukemia tumor suppressor gene inactivation in the mouse

Introducing dominant oncogenic alterations uncovered in human myeloid malig nancies into the mouse germline provides a powerful approach for studying l eukemogenesis. However, little is known about how gene inactivation contrib utes to the development of myeloid malignancies. We describe how Nf1 mutant ,mice provide one example in which disrupting a tumor suppressor gene has b een used to generate an informative murine leukemia model. We also discuss how chromosome engineering technologies are being harnessed to model the se gmental deletions found in)myeloid malignancies, and how these approaches c an be combined with retrovirally medicated insertional mutagenesis to gener ate new models and for gene discovery.