Altered sensitivity to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate of DNA polymerase alpha from leukemic blasts of acute lymphoblastic leukemia.
DNA polymerase alpha from the leukemic cells of acute lymphoblastic leukemia (ALL) was found to be more resistant to the inhibition by 1-beta-D-arabinofuranosylcytosine 5'-triphosphate than that from acute myeloblastic leukemia (AML). Apparent Ki values for 1-beta-D-arabinofuranosylcytosine 5'-triphosphate of DNA polymerase alpha from eight patients with ALL [26.7 +/- 7.1 (S.D.) microM] were 5 times higher than those from nine patients with AML [5.2 +/- 1.3 microM]. In contrast, apparent Km values for a normal substrate deoxycytidine 5'-triphosphate of DNA polymerase alpha preparations from either AML and ALL were almost identical (9.4 to 10.9 microM). Likewise, apparent Ki values for another arabinoside analog, 9-beta-D-arabinofuranosyladenine 5'-triphosphate, of DNA polymerase alpha from blasts of seven patients with ALL (16.9 +/- 6.9 microM) were significantly higher than those from patients with AML (3.8 +/- 0.5 microM). These results indicate that DNA polymerase alpha from ALL blast cells has a decreased affinity to the arabinoside analogs of deoxynucleotide triphosphate. The sensitivity of DNA polymerase alpha of blast cells to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate may be one of the determinants of the clinical response to 1-beta-D-arabinofuranosylcytosine treatment.
D001085:Arabinofuranosylcytosine Triphosphate / Q000494:pharmacology*; D001088:Arabinonucleotides / Q000494:pharmacology*; D004256:DNA Polymerase I / Q000378:metabolism; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004258:DNA Polymerase III / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000201:enzymology*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology; D019384:Nucleic Acid Synthesis Inhibitors
D001088:Arabinonucleotides; D019384:Nucleic Acid Synthesis Inhibitors; D001085:Arabinofuranosylcytosine Triphosphate; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004258:DNA Polymerase III