With this proposal we hope to initiate investigations of two genes recently cloned from chromosomal translocations in human leukemias: (a) the BCL3 (B cell leukemia-3) which is involved in the activation of the C-MYC gene; and (b) the TCL5 (T cell leukemia-5) gene, a possible new oncogene that becomes activated by either chromosomal translocations involving antigen receptor genes or by deletions. Our goal is to study translocations involving these genes with regards to biological actions and mechanisms of oncogene activation. Analysis of leukemic cell lines containing BCL3 and TCL5 translocations will determine the relative contributions of transcriptional and post-transcriptional mechanisms to the deregulated expression of the involved oncogenes (C-MYC, TCL5), providing information needed for selecting appropriate cloned DNAs for gene transfer experiments. Genomic clones isolated from translocation regions will then be introduced into B and T cell lines, and DNA fragments sufficient for providing deregulated oncogene expression will be identified. Using these cloned DNAs directly or in expression vector form, the biological actions of translocations involving BCL3 and TCL5 will be explored in various cultured cells, as well as in transgenic mice. These investigations will begin to define the roles of BCL3 and TCL5 translocations in the pathogenesis of human leukemias and lymphomas.
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