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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ross, D. D. Articles by Schiffer, C. A. Search for Related Content PubMed PubMed Citation Articles by Ross, D. D. Articles by Schiffer, C. A. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Metabolism of ara-C by blast cells from patients with ANLL DD Ross, BW Thompson, CC Joneckis, SA Akman and CA Schiffer The dose-response relationship between extracellular concentration of cytosine arabinoside (ara-C) and intracellular formation of the putative active metabolites of ara-C [ara-C incorporation into DNA and intracellular pools of ara-C in triphosphate form (ara-CTP)] was investigated in blast cells obtained from patients with acute nonlymphocytic leukemia (ANLL) by exposing these cells in vitro to 10, 100, or 1,000 nmol/L of ara-C. We studied 23 untreated patients who subsequently achieved complete remission (CR) with a regimen using daunorubicin and conventional doses of ara-C (ara-C-sensitive group), and 30 patients judged to be ara-C-resistant either by failing initial induction therapy (16 patients) or by having relapsed on an ara-C- containing maintenance regimen (14 patients). In both patient groups, ara-C incorporation into DNA and intracellular ara-CTP both displayed statistically significant increases in response to increasing extracellular concentrations of ara-C (P = .0001 in both cases), with the rate of increase of ara-CTP greater than that of ara-C incorporation. Moreover, blast cells from all patients, even those who were most clinically resistant to ara-C, were able to form ara-CTP and to incorporate ara-C into DNA. Each tenfold increment in extracellular ara-C concentration caused an 8.5-fold increase in ara-CTP, but only a 3.6-fold increase in ara-C incorporation into DNA. Thus, the efficiency of incorporation of ara-C into DNA (defined as the ratio of ara-C incorporation to ara-CTP pools) decreased by 58% with each tenfold increment in the extracellular concentration of ara-C (P less than .0001), presumably as a result of the inhibitory effect of ara-CTP on DNA polymerase. Using an analysis of covariance, modest differences were found in the levels of the ara-C metabolite variables in the ara-C- sensitive group as compared with the resistant group. However, because there was considerable overlap in ara-C metabolite formation among the patient groups, it was not possible to predict clinical outcome by these in vitro assessments of ara-C metabolism. Volume 68, Issue 1, pp. 76-82, 07/01/1986 Copyright © 1986 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Jahns-Streubel, C. Reuter, U. Auf der Landwehr, M. Unterhalt, E. Schleyer, B. Wormann, T. Buchner, and W. Hiddemann Activity of Thymidine Kinase and of Polymerase alpha  as Well as Activity and Gene Expression of Deoxycytidine Deaminase in Leukemic Blasts Are Correlated With Clinical Response in the Setting of Granulocyte-Macrophage Colony-Stimulating Factor-Based Priming Before and During TAD-9 Induction Therapy in Acute Myeloid Leukemia Blood, September 1, 1997; 90(5): 1968 - 1976. [Abstract] [Full Text] [PDF]

	Copyright © 1986 by American Society of Hematology         Online ISSN: 1528-0020