Abstract

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?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA014054-16
Application #
3163860
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1980-01-01
Project End
1992-07-31
Budget Start
1989-08-25
Budget End
1990-07-31
Support Year
16
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Karolinska Institute
Department
Type
DUNS #
350582235
City
Stockholm
State
Country
Sweden
Zip Code
171 77

  Publications

Silva, S; Wang, Y; Babonits, M et al. (1997) Spontaneous development of plasmacytomas in a selected subline of BALB/cJ mice. Eur J Cancer 33:479-85
Szekely, L; Pokrovskaja, K; Klein, G (1997) Differential expression of nucleoskeleton- and cytoskeleton-associated proteins in Burkitt lymphoma-derived and Epstein-Barr virus-immortalized lymphoblastoid cell lines. Cell Growth Differ 8:599-609
Sumegi, J; Wang, J Y; Zhen, D K et al. (1996) The construction of a yeast artificial chromosome (YAC) contig in the vicinity of the Usher syndrome type IIa (USH2A) gene in 1q41. Genomics 35:79-86
Allikmets, R; Kashuba, V I; Huebner, K et al. (1996) Mapping of 22 Notl linking clones on human chromosome 3 by polymerase chain reaction and somatic cell hybrid panels. Chromosome Res 4:33-7
Sithanandam, G; Latif, F; Duh, F M et al. (1996) 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region. Mol Cell Biol 16:868-76
Szekely, L; Pokrovskaja, K; Jiang, W Q et al. (1996) The Epstein-Barr virus-encoded nuclear antigen EBNA-5 accumulates in PML-containing bodies. J Virol 70:2562-8
Szeles, A; Bajalica-Lagercrantz, S; Lindblom, A et al. (1996) Mapping of a new MAP kinase activated protein kinase gene (3PK) to human chromosome band 3p21.2 and ordering of 3PK and two cosmid markers in the 3p22-p21 tumour-suppressor region by two-colour fluorescence in situ hybridization. Chromosome Res 4:310-3
Vorobieva, N; Protopopov, A; Protopopova, M et al. (1995) Localization of human ARF2 and NCK genes and 13 other NotI-linking clones to chromosome 3 by fluorescence in situ hybridization. Cytogenet Cell Genet 68:91-4
Axelson, H; Henriksson, M; Wang, Y et al. (1995) The amino-terminal phosphorylation sites of C-MYC are frequently mutated in Burkitt's lymphoma lines but not in mouse plasmacytomas and rat immunocytomas. Eur J Cancer 31A:2099-104
Kashuba, V I; Szeles, A; Allikmets, R et al. (1995) A group of NotI jumping and linking clones cover 2.5 Mb in the 3p21-p22 region suspected to contain a tumor suppressor gene. Cancer Genet Cytogenet 81:144-50

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