The goal of this project is to characterize the molecular mechanisms of cell growth control in T cells, and to identify the defects in the leukemia/ lymphoma cells. The structure and function of mouse IL-2 induced genes will be characterized by Northern blot analysis or DNA sequencing. The promoter binding factor which must be activated by IL-2 will be isolated and characterized by gel shift assay. The role of these genes and their products in the regulation of T cell proliferation will be elucidated using antibodies or antisense oligonucleotides. In addition, metabolic inhibitors which arrest cells at various phases of the cell cycle will be used to characterize normal human T cells and identify the defects in leukemia/lymphoma cells. Normal cells and leukemia/ lymphoma cells will be characterized using MTT or propidium iodide. The differences among proteins in the arrested cells of both types will be characterized by chemicals on two dimensional gel electrophoresis. The different proteins will be further characterized. Molecular constructs joining toxin genes with promoters of the genes abnormally activated in leukemia/lymphoma cells will be developed. This will allow the prevention of growth of the leukemia/lymphoma cells efficiently and selectively in vitro. This project may provide new insights into the regulatory mechanisms of T cell proliferation, and enhance understanding of the defects seen in the regulation of a variety of leukemia/lymphoma cells. It may yield new ideas regarding the development of rational therapeutic approaches in patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA052835-02
Application #
3459980
Study Section
Experimental Immunology Study Section (EI)
Project Start
1991-08-01
Project End
1996-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104