Cloned DNA sequence of human terminal transferase and monoclonal human TdT antibodies will be used to explore questions directly related to the biological activity of this enzyme. These questions are: 1. Is TdT generally mutagenic in any prokaryotic or eukaryotic system that contains it? 2. Is the structure of TdT related to its cellular location and regulation of its activity? 3. Is the promoter sequence for TdT specific for tissues and stage of differentiation? 4. Is TdT specifically mutagenic in systems that normally contain it? Answers to these questions will help to understand the normal role of terminal transferase in the immunopoietic system and its abnormal expression in acute leukemias.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA042081-03
Application #
3482522
Study Section
Biochemistry Study Section (BIO)
Project Start
1986-09-01
Project End
1991-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20852
Chang, L M; Bollum, F J (1990) Multiple roles of divalent cation in the terminal deoxynucleotidyltransferase reaction. J Biol Chem 265:17436-40
Childs, C C; Hirsch-Ginsberg, C; Walters, R S et al. (1989) Myeloid surface antigen-positive acute lymphoblastic leukemia (My+ ALL): immunophenotypic, ultrastructural, cytogenetic, and molecular characteristics. Leukemia 3:777-83
Chang, L M; Rusquet-Valerius, R; Roy, N K et al. (1989) Is terminal deoxynucleotidyl transferase an intracellular mutagen? Biochem Biophys Res Commun 165:271-7
Chang, L M; Rafter, E; Rusquet-Valerius, R et al. (1988) Expression and processing of recombinant human terminal transferase in the baculovirus system. J Biol Chem 263:12509-13
Childs, C C; Hirsch-Ginsberg, C; Culbert, S J et al. (1988) Lineage heterogeneity in acute leukemia with the t(4;11) abnormality: implications for acute mixed lineage leukemia. Hematol Pathol 2:145-57
Hirsch-Ginsberg, C; Childs, C; Chang, K S et al. (1988) Phenotypic and molecular heterogeneity in Philadelphia chromosome-positive acute leukemia. Blood 71:186-95