Friend helper virus (F-Eco) is a murine retrovirus which can induce a variety of hematopoietic neoplasms. This virus is being used as a model to study mechanisms of leukemogenesis. 1. Genetic Studies: Crosses between AKR and other strains indicated that AKR mice carry at least two genes other than inherited ecotropic retroviruses which predispose them to lymphoma after inoculation with F-Eco. Further genetic studies are being done to localize these genes and determine their relationship to other oncogenes. 2. Molecular studies: Using a provirus-cellular DNA junction fragment cloned from one F-Eco induces myeloid leukemia, we found that several other F-Eco induced lymphomas and myeloid leukemias have an F-Eco provirus integrated in the same region of cellular DNA, designated Fis-1. This common integration region maps very close to Int-2, an oncogene involved in murine mammary carcinomas. On a molecular level, Fis-1 and Int-2 are clearly distinct. Studies are underway to determine if Fis-1 represents a new oncogene involved in lymphoid and myeloid malignancies, or whether F-Eco integration at this site activates Int-2. We are also beginning to investigate the human homologue of Fis-1 which might be involved in human B cell lymphomas, some of which have a translocation involving the region of chromosome 11 which contains the human homologue of Int-2. 3. Significance. F-Eco provides a model system to study molecular events in leukemogenesis. Because of the high degree of conservation of oncogenes, these studies are likely to shed light on genes involved in human cancers.
