On-going studies on the transformation of cells by Abelson murine leukemia virus (A-MuLV) and the mechanism of inducing immunoglobulin gene rearrangements will be continued. Both lines of investigation relate to early steps of B-lymphoid cell differentiation. In the A-MuLV program, three major approaches are planned: (1) mapping the regions of the cellular c-abl gene that suppress its inherent oncogenic activity and studying the regions required for oncogenesis; (2) localizing by immunofluorescence techniques the abl-related normal and oncogenic proteins within normal and malignant cells and (3) developing mouse models in which the bcr-abl fused gene, from chronic myelogenous leukemic cells, is able to induce myeloid proliferation. In the immunoglobulin gene rearrangement program, two major approaches are planned: (1) finding and characterizing the gene (RAG-1) that induces rearrangement of implanted immunoglobulin genes in fibroblasts; (2) developing a better understanding of the molecular and enzymatic events of gene rearrangement and probing the regulatory events that determine which genes will rearrange at a given stage of immunodifferentiation and how the events are integrated. These studies should increase understanding of events in immunodifferentiation and help to understand how they are deranged during oncogenesis. They should also help in understanding immunopathogenesis, especially defects in lymphocyte development.
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