Genetic heterogeneity in acute myeloid leukemia: maximizing information flow from MuLV mutagenesis studies

The study of myeloid leukemia induced by slow transforming murine leukemia viruses (MuLV) in the laboratory mouse has led to discovery of many importa nt genes with critical roles in regulating the growth, death, lineage deter mination and development of hematopoietic precursor cells. This review prov ides an overview of the susceptible strains and virus isolates that cause a cute myeloid leukemia (AML) in mice. In addition, newer methodologies, invo lving the use of the polymerase chain reaction, that have been used to iden tify cancer genes mutated by proviral insertion in mouse models, will be di scussed. As cancer is a multi-gene disease, a system in which pairs of onco genic mutations are classified as redundant, neutral or synergistic is desc ribed. The potential to combine MuLV mutagenesis with recent advances in mo use transgenesis in order to model specific forms of myeloid leukemia or ge netic pathways common in human AML will be discussed. Finally, a general st rategy for maximizing these genetically rich models to foster a better unde rstanding of AML physiology and developing therapies is proposed.