The objective of this research is to investigate the function of the v-myb oncogne in the transformation of hematopoietic cells and to determine the relationship of the transforming function of v-myb to the normal function of its cellular homologue, c-myb. Avian myeloblastosis virus (AMV) which carries the prototypic v-myb oncognee has a target cell populations which appears to be restricted to the macrophage lineage in the normal chicken host. Expression of high levels of c-myb have been found in macrophage progenitors which suggests a relationship between the target cells for v-myb and expression of c-myb in its normal developmental context. High levels of c-myb have also been reported for T-cells and in several types of leukemia. To further investigate the relationsip between hematopoietic development, expression of c-myb and susceptibility to transformation by the myb oncognee, a murine retrovirus will be constructed carrying the v-myb oncogene identical to that encoded by AMV. The target cells for this new virus will be determined both in vivo and in vitro and compared to the avian system. The new virus will be used to investigate examine the effect of myb on the factor dependence of various factor dependent cell lines. The long term bone marrow culture system (Dexter cultures) will be used to analyze the effects of v-myb on the macrophage progenitors and an anti-sense myb virus will be used in experiments to determine the role of c-myb in macrophage differentiation. Following the in vitro experiments, in vivo experiments will have conducted using the reconstitution of anemic W/Wv mice which have a hematopoietic stem cell defect which permits replacement of the resident stem cells with stem cells of donor origin. The stem cells for reconstitution will be manipulated using both sense and anti-sense myb constructs. The experiments will allow the effects on both the myeloid and lymphoid lineages to be examined.
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