Saturation of intracellular cytosine arabinoside triphosphate accumulation in human leukemic blast cells

• Published in: Leukemia Research Vol. 14; no. 5; pp. 475 - 479
• Main Authors: Jamieson, Gary P., Snook, Marie B., Wiley, James S.
• Format: Book Review Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1990; Elsevier Science
• Subjects: Acute Disease; acute leukemia, nucleoside transport, deoxycytidine kinase, nitrobenzylthioinosine, labeling index; Antineoplastic agents; Arabinofuranosylcytosine Triphosphate - pharmacokinetics; Arabinonucleotides - pharmacokinetics; Binding Sites; Biological and medical sciences; Biological Transport; blast cells; Cell Membrane - metabolism; Cytarabine - administration & dosage; Cytarabine - metabolism; Cytosine arabinoside; cytosine arabinoside triphosphate; Deoxycytidine Kinase - metabolism; Extracellular Space - metabolism; General aspects; Humans; Leukemia - enzymology; Leukemia - metabolism; Lymphocytes - metabolism; Medical sciences; Nucleosides - metabolism; Pharmacology. Drug treatments; Phosphorylation; Thioinosine - analogs & derivatives; Thioinosine - metabolism; Tumor Cells, Cultured - enzymology; Tumor Cells, Cultured - metabolism; AML; NBMPR; ALL; Cytosine arabinoside; araCDP; araCTP; acute leukemia, nucleoside transport, deoxycytidine kinase, nitrobenzylthioinosine, labeling index; araC; araCMP; Antineoplastic agent; Human; Phosphorylation; Enzyme; Saturation; Malignant hemopathy; In vitro; Deoxycytidine kinase; Antimetabolic; Membrane transport; Biological accumulation; Pyrimidine nucleoside; Tumor cell; Acute myelocytic leukemia
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/0145-2126(90)90035-8

Accumulation of cytosine arabinoside triphosphate (araCTP) from a range of cytosine arabinoside (araC) concentrations (1–50 μM) was measured during incubations of leukemic cells freshly isolated from patients with acute leukemia. In all but one patient, increments in extracellular araC above 10 μM did not increase intracellular araCTP levels. This maximal level of araCTP accumulation ranged from 254 to 1607 pmol/10 7 cells attained after 1 h incubation and did not correlate with either the number of nucleoside transporters on the cell membrane or the V max of araC phosphorylation in cell free extracts. Extremely low araCTP accumulation (103 pmol/10 7 cells/h at 50 μM araC) was observed in an AML patient with the unusual finding of micromyeloblasts. These cells also had very low numbers of nucleoside transport sites (< 500 sites/cell) and were mitotically inactive. The unique feature of the myeloblasts from this patient was that intracellular araCTP accumulation showed a linear dependence on extracellular araC up to 50 μM with no evidence of saturation.