Myeloid lineage leukemias represent a high proportion of leukemias in the human population. Some of these leukemias are consistently associated with chromosomal translocation, deletions and gene amplifications in which oncogenes have been implicated. Our group has found a useful model in the murine hemopoietic system for studying these types of leukemias. The overall goal is to look at the transforming effects of various oncogenes on mouse cells in vivo and in vitro with a particular emphasis on their cooperative effects of oncogenes on cells of the myeloid lineage. The laboratory, because of its experience in constructing and testing retroviruses, uses naturally occurring, as well as genetically engineered retroviruses, as vehicles for introducing oncogenes into cells. We are taking advantage of two modes for leukemia induction 1) one in which oncogenes or potential oncogenes are introduced via replication defective retrovirus vectors and are allowed to transform cells directly, and 2) one in which replication competent viruses, such as Moloney murine leukemia virus, are introduced and spread through mice until they activate an oncogene by insertional mutagenesis. These studies have led to the discovery of two experimental protocols for induction of myeloid tumors in pristane primed mice. In one system using the myc gene containing retrovirus, the tumors that arise are mature macrophage cells whereas in the other systems, using Moloney murine leukemia virus, the cells are rather immature myelomonocyte cells. Some newer studies include the construction and biological testing of viruses encoding potential oncogenes such as the transferrin receptor.
