Cellular Metabolism and T-ALL Specificity of Arabinosylguanine: a Review

  • W. Plunkett
  • V. Gandhi
  • C. O. RodriguezJr.
  • M. J. Keating
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 39)


A metabolic disorder resulting from deficiency of a purine nucleoside catabolizing enzyme first focused attention on the specific sensitivity of immature T-cells to deoxyguanosine nucleotides. Recognition that T-cell malignancies might have similar sensitivities coupled with the clinical success of other arabinosyl nucleosides subsequently led to the preclinical evaluation of arabinosylguanine for this purpose. Strong correlations between the specificity of arabinosylguanine for immature T-cells was explained by the favorable anabolism of the drug in cell lines and primary human leukemia cells in vitro. Development of a prodrug of ara-G, compound 506U, has now permitted clinical trials. Preliminary reports indicate that the laboratory studies were predictive of the spectrum of clinical activity; a high initial response rate was seen in T-cell malignancies. Pharmacology studies in circulating leukemia cells during therapy demonstrated that the peak accumulation of the active metabolite, arabinosylguanine triphosphate, was strongly correlated with clinical response. Strategies to maximize accumulation of the triphosphate in non-T-cell malignancies are now being designed.


Adenosine Deaminase Purine Nucleoside Purine Nucleoside Phosphorylase Compound 506U Cellular Pharmacokinetic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • W. Plunkett
    • 1
  • V. Gandhi
    • 1
  • C. O. RodriguezJr.
    • 1
  • M. J. Keating
    • 2
  1. 1.Departments of Clinical InvestigationThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Departments of HematologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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