Human lymphoid leukemias are phenotypically heterogenous diseases, the subtypes of which appear to represent clonal cells that are arrested at specific stages of lymphoid ontogeny. Individual phenotypes of leukemia are defined by cell surface antigens, programmed gene rearrangements and selected enzyme markers. One of these markers, terminal deoxynucleotidyl transferase, is expressed only in normal prelymphocytes and their neoplastic counterparts. It has been proposed that terminal transferase activity is responsible for addition of N regions (extra random nucleotides) to DNA during rearrangement of immunoglobulin heavy chain genes or T cell receptor beta genes. Recently, cDNAs coding for human terminal transferase have been cloned and used to isolate the gene coding for this enzyme. The terminal transferase gene is large (-50 kb) and appears to exist in low copy number in normal tissues. The goal of this proposal is to determine structure of the terminal transferase gen in normal and neoplastic tissues. Preliminary data suggest that the structure of the gene is altered in various tissues. This study will assess tissue specific, individual and leukemia-associated polymorphisms in the gene and its regulatory region, using Southern genomic blotting and in situ hybridization techniques. The expression of terminal transferase mRNA, antigen and activity will be assessed in selected cells and correlated with the structural data derived from studies of the gene. Integration of these data will yield a comprehensive picture of structure/ function correlates of this gene in normal and leukemic cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA001416-03
Application #
2084013
Study Section
Cancer Institutional Fellowship Review Committee (CT)
Project Start
1989-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1995-06-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Biochemistry
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599