Uniqueness of Deoxyribonucleotide Metabolism in Human Malignant T Cell Lines
Inherited deficiencies of the purine metabolic enzymes, adenosine deaminase (ADA) and purine nucleoside Phosphorylase (PNP) specifically impair the growth and development of the lymphoid system in human beings1,2. We have proposed that lymphospecific toxicity in these diseases might result from the selective phosphorylation and trapping by T lymphocytes of the adenosine deaminase substrate deoxyadenosine (AdR) and the purine nucleoside Phosphorylase substrate deoxyguanosine (GdR), with the subsequent formation of toxic deoxyribonucleoside triphosphates3. We further proposed that the phosphorylation was mediated by the lymphospecific enzyme deoxycytidine kinase, for which AdR and GdR are substrates, albeit poor ones4. This hypothesis was difficult to test in. vivo because of the severe lymphopenia observed in untreated enzyme deficient patients. In an effort to find a relevant in vitro model system, we therefore turned to human malignant T lymphoblasts derived from patients with T cell leukemia and a mediastinal mass. These cells are conveniently available as continuous lines and share certain antigenic and biochemical characteristics with normal primitive thymocytes5,6.
KeywordsThymidine Kinase Adenosine Deaminase Purine Nucleoside Phosphorylase Adenosine Kinase Deoxycytidine Kinase
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