PURINE NUCLEOTIDE PYROPHOSPHORYLASES IN 6-MERCAPTOPURINE-SENSITIVE AND -RESISTANT HUMAN LEUKEMIAS.

Abstract

Summary The present study was undertaken to determine whether a loss of the enzyme activity responsible for converting 6-mercaptopurine, hypoxanthine, and guanine to their ribonucleotides correlates with resistance to 6-mercaptopurine in human leukemic leukocytes. Six normal and 26 leukemic patients were studied. Fifteen of the leukemic patients were felt to be clinically resistant to 6-mercaptopurine. Only one of these showed a significant reduction in inosinic-guanylic pyrophosphorylase activity. All other leukemic patients showed enzyme activities similar to those of normal patients, except that the leukemic patients had an adenylic pyrophosphorylase activity 2–3 × that of normal leukocytes. Thus, loss of inosinic-guanylic pyrophosphorylase did occur in human leukemia, but it did not explain most cases of resistance to 6-mercaptopurine in the leukemic patients studied.