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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA060181-04
Application #
2100863
Study Section
Special Emphasis Panel (SRC)
Project Start
1992-09-15
Project End
1997-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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