Many B-cell leukemias and lymphomas have characteristic chromosomal abnormalities. The t(14;18) translocation is found in follicular lymphoma, the t(11;14) translocation in diffuse small and large cell lymphoma, and the t(8;14), t(2;8) or t(8;22) translocation is seen in Burkitt's lymphoma or other high grade lymphoproliferative malignancies. It was previously shown that rearrangements of the bcl-2 gene are associated with the t(14;18) translocation, rearrangements of the bcl-1 gene with t(11;14) translocation, and rearrangements of the c-myc oncogene with Burkitt's lymphoma. I intend to study the evolution of B-cell malignancies. I hypothesize that rearrangements of the bcl-2 gene lead to the occurrence of additional chromosomal abnormalities. I plan to use cDNA to screen patient samples for translocation involving the bcl-2, bcl-1, or c-myc gene as well as additional alterations of these genes. I will rescreen specimens from patients during the course of their disease. Cell lines from patient samples will be developed. Genomic libraries will be prepared in order to clone the involved loci. The cloned rearrangements will be characterized by restriction enzyme mapping, analysis of the nucleotide sequence, and I will study their transcripts. I further want to investigate whether the infection of hematopoietic cells with the bcl-2 and the c-myc oncogenes in retrovirus vectors results in malignant transformation. In addition, I want to establish whether infection of B-cells, T-cells and other hematopoietic cells with retroviruses containing the bcl-2 and the c-myc oncogenes results in the establishment of continuous cell lines. These experiments should provide important insights into the mechanisms involved in the control of B- and T-cell proliferation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Physician Scientist Award (K11)
Project #
1K11CA001279-01
Application #
3085705
Study Section
(SRC)
Project Start
1987-09-15
Project End
1992-09-14
Budget Start
1987-09-15
Budget End
1988-09-14
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Gauwerky, C E; Huebner, K; Isobe, M et al. (1989) Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia. Proc Natl Acad Sci U S A 86:8867-71
Gauwerky, C E; Haluska, F G; Tsujimoto, Y et al. (1988) Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene. Proc Natl Acad Sci U S A 85:8548-52