BCL1 leukemia is the first B cell leukemia to be described in mice having arisen spontaneously in an elderly BALB/c mouse. One cell transferred to a syngeneic recipient causes progressive leukemia that is always detectable by 12 weeks and is followed by progressive tumor growth and death. Mice rendered chimeric at the H-2 locus by lethal X-irradiation followed by injection of T cell depleted allogeneic bone marrow allow progressive growth of subsequently injected BCL1 cells. However, after 6 weeks, the tumor recedes and the mice appear tumor-free as judged by idiotype analysis of blood cells, white blood count, and spleen size. Disease does not occur for as long as the mice have been followed (8 months). Nevertheless, cell transfer studies indicate a relatively large tumor load in the spleen (10-6 - 10-7 cells). We will study the biology of tumor dormancy in attempts to answer the following questions: 1) What is the cell cycle status of the dormant cells? 2) Are they different from the starting population as judged by immunophenotype, response to lymphokines and karyotype? 3) What are the host defense mechanisms that are required to induce dormancy? 4) What is the natural history of dormancy, e.g. do dormant BCL1 cells eventually die or do they begin to grow when immune responsiveness decreases with age? 5) What perturbations can initiate tumor growth? 6) Can immunotoxins specific to BCL1 eliminate this dormant population in vivo? With regard to a syngeneic model of tumor dormancy, immunity to the BCL1 tumor has been generated in both BALB/c mice previously immunized with purified BCL1-IgMlambda and in non-immunized congenic mice (B.A. 20) that differ at the IgH locus. We will further develop these 2 model systems to study tumor dormancy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042228-03
Application #
3183209
Study Section
Pathology B Study Section (PTHB)
Project Start
1986-09-30
Project End
1989-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390