This project is based on our earlier findings concerning the role of the IgH/myc juxtaposition in the genesis of murine plasmacytoma (MPG), rat immunocytoma (RIC) and human Burkitt lymphoma (BL) and the role of chr 15 trisomy in murine T-cell leukemia. This field has been largely initiated by our cytogenetic findings and derived working hypotheses, made under this grant. It is now pursued at numerous laboratories. We have chosen to concentrate our continued work on a few selected topics, where our laboratory has special experience, materials and/or has developed new working hypotheses. Our current aims are the following: I. CYTOGENETIC AND BIOLOGICAL STUDIES I.1. Plasmacytogenesis. a) Characterization of the murine plasmacytoma (MPC) precursor cell: b) Studies on the accelerating effect of A-MuLV on PC-genesis; c) Studies on the level of genetically determined PC- resistance in chimeric mice. I.2. Lymphomagenesis. Does consistutively expressed v-suppression: a) Does the normal fibroblast derived chromosome 15 contain a gene that counteracts tumorigenicity of T- leukemia cells with retrovirally rearranged c-myc or pvt-17: b) Do normal cells of different lineages carry suppressor genes on different chromosomes?: b) Do normal cells of different lineages carry suppressor genes on different chromosomes? c) Is suppressor loss involved in lymphoagenesis in conventional F1 and in transgenic mice?; d) Studies on a non-tumorigenic Burkitt lymphoma (BL) revertant. II.4. Studies on the decay of c-myc mRNA in normal and IgH/myc translocation-carrying cells; Ii.5 Continued studies on the rat immunocytoma associated IgH/myc translocation; II.6. Molecular studies of c-myc translocations to the functional heave chain producing chromosome in double heterozygous MPCs; II.7 Relationship between c-myc amplification and tumor progression in an experimentally modulatable mouse tumor system; II.8. Continued structural and functional studies on the B-myc gene; II.9 IgH-locus associated illegitimate translocations in pro-B-cells: a model for the IgH/myc translocation in Burkitt lymphoma?
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