Altered sensitivity to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate of DNA polymerase alpha from leukemic blasts of acute lymphoblastic leukemia

Cancer Res. 1982 Feb;42(2):649-53.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabinofuranosylcytosine Triphosphate / pharmacology*
  • Arabinonucleotides / pharmacology*
  • DNA Polymerase I / metabolism
  • DNA Polymerase II / antagonists & inhibitors*
  • DNA Polymerase III / metabolism
  • Drug Resistance
  • Humans
  • Kinetics
  • Leukemia, Lymphoid / enzymology*
  • Leukemia, Myeloid, Acute / enzymology
  • Leukocytes / drug effects*
  • Leukocytes / enzymology
  • Nucleic Acid Synthesis Inhibitors*


  • Arabinonucleotides
  • Nucleic Acid Synthesis Inhibitors
  • Arabinofuranosylcytosine Triphosphate
  • DNA Polymerase I
  • DNA Polymerase II
  • DNA Polymerase III