GENETIC EXPRESSION OF ADENOSINE DEAMINASE (ADA) IN HUMAN LYMPHOID MALIGNANCIES: 67

Abstract

The activity of the purine salvage enzyme, ADA, is 10 to 50-fold higher in T lymphoblasts than in mature lymphocytes and has been used as an enzymatic marker of T-lymphoblastic malignancies. We have asked whether the level of ADA activity in leukemic cells is controlled at the transcriptional or post-transcriptional level. Total cellular RNA was isolated from leukemic cell lines derived from patients with acute T cell leukemia and with T cell leukemia of mature phenotype, as well as from the peripheral blood of 4 patients with non-T cell ALL and 3 patients with chronic lymphocytic leukemia (CLL). Hybridization with a cDNA probe specific for ADA revealed 1.8 and 5.8 Kb bands on Northern blots which were present in all cell types examined. Specific ADA mRNA levels were quantitated by densitometry tracings of Northern blots and compared with both ADA specific activity and ADA protein, as determined by a solid-phase radioimmunoassay. There was a strong correlation between the steady state levels of mRNA and ADA immunoreactive material in all cells examined (correlation coefficient value of 0.76). T lymphoblasts contained 2 to 4-fold more ada mRNA than did the mature T cell lines, 5 to 10-fold more than CLL cells, and 1.5 to 4-fold more than non-T cell ALL cells. ADA specific activity also tended to correlate with mRNA levels. We conclude that the high levels of ADA in T lymphoblasts result from increased transcription of the ADA gene or, possibly, from increased ADA mRNA stability in these cells.