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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)

Abstract

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.

Keywords

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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References

  1. 1.
    Evans JS, Musser EA, Mengel GD, Forsblad KR, Hunter JH (1961) Proc Soc Exptl Biol Med 106: 350Google Scholar
  2. 2.
    Hubert-Habart M, Cohen SS (1962) Biochim Biophys Acta, 59: 468–471PubMedCrossRefGoogle Scholar
  3. 3.
    Reist EJ, Goodman L (1962) Biochemistry, 3: 1518Google Scholar
  4. 4.
    Elion GB, Rideout JL, DeMiranda, P., Collins, P, Bauer DJ (1975) Ann N Y Acad Sci 255: 468PubMedCrossRefGoogle Scholar
  5. 5.
    Krenitsky TA, Koszalka W, Tuttle JB, Rideout JL, Elion GB (1981) Carbohydrate Res 97: 139–146CrossRefGoogle Scholar
  6. 6.
    Brink JJ, LePage GA (1964) Cancer Res 24: 312–318PubMedGoogle Scholar
  7. 7.
    Giblett E (1975) Lancet 1: 1010–1013PubMedCrossRefGoogle Scholar
  8. 8.
    Cohen A, Doyle D, Martin DW, Ammann AJ (1976) N Engl J Med 295: 1449–1454PubMedCrossRefGoogle Scholar
  9. 9.
    Cohen A, Gudas LJ, Ammann AJ, Martin DWJ (1978) Clin. Invest 61: 1405–1410CrossRefGoogle Scholar
  10. 10.
    Mitchell BS, Mejias E, Daddona PE, Kelly WN (1978) Proc Nat Acad Sci USA 75: 5011–5014PubMedCrossRefGoogle Scholar
  11. 11.
    Gelfand EW, Lee JW, Dosch H-M (1979) Proc Nat Acad Sci USA 76: 1998–2002PubMedCrossRefGoogle Scholar
  12. 12.
    Cohen A, Lee JWW, Dosche H-M, Gelfand EWJ (1980) Immunol 125: 1578–1582Google Scholar
  13. 13.
    Gudas LJ, Ullman B, Cohen A, Martin DW (1975) Cell 14: 531–538CrossRefGoogle Scholar
  14. 14.
    Sheen MR, Kim BK, Parks RE (1968) Mol Pharmacol 4: 293–297PubMedGoogle Scholar
  15. 15.
    Kazmers IS, Mitchell BS, Daddona PE, Wotring LL, Townsend LB, Kelly WN (1981) Science 214: 1137–1139PubMedCrossRefGoogle Scholar
  16. 16.
    Gelfand EW, Cohen A, How A, Dosch H-M (1980) Clin Res 28: 346Google Scholar
  17. 17.
    Cohen A, Lee JWW, Gelfand EW (1983) Blood 61: 660–666PubMedGoogle Scholar
  18. 18.
    Ullman B, Martin DWJ (1984) Clin Invest 74: 951–955CrossRefGoogle Scholar
  19. 19.
    Shewach DS, Daddona PE, Ashcraft E, Mitchell, BS (1985) Cancer Res 45: 1004–1014Google Scholar
  20. 20.
    Verhoef V, Fridland A (1985) Cancer Res 45: 3646–3650PubMedGoogle Scholar
  21. 21.
    Sidi Y, Edwards NL, Winkler C, Bunn P, Mitchell BS (1985) Br J Haematol 61: 125–134PubMedCrossRefGoogle Scholar
  22. 22.
    Ono K, Ohashi A, Yamamoto A, Matsukage A, Takahasi T, Saneyoshi M, Ueda T (1979) Cancer Res 39: 4673–4680PubMedGoogle Scholar
  23. 23.
    Gandhi V, Mineishi S, Huang P, Chapman A, Chen F, Nowak B, Chubb S, Hertel LW, Plunkett W (1995) Cancer Res 55: 1517–1524PubMedGoogle Scholar
  24. 24.
    Shewach DS, Mitchell BS (1989) Cancer Res 49: 6498–6502PubMedGoogle Scholar
  25. 25.
    Lambe CU, Averett DR, Paff MT, Reardon JE, Wilson JE, Krenitsky TA (1995) Cancer Res 55: 3352–3356PubMedGoogle Scholar
  26. 26.
    Prus KL, Averett DR, Zimmerman TP (1990) Cancer Res 50: 1817–1821PubMedGoogle Scholar
  27. 27.
    Barker J, Lewis RA (1981) Biochim Biophys Acta 658: 111–123PubMedGoogle Scholar
  28. 28.
    Wang L, Karlsson A, Amer ESJ, Ericksson SJ (1993) Biol Chem 268: 22847–22852Google Scholar
  29. 29.
    Carson DA, Kaye J, Seegmiller JE (1977) Proc Nat Acad Sci USA 74: 5677–5681PubMedCrossRefGoogle Scholar
  30. 30.
    Kurtzberg J, Wiley J, Reese M, Elion G, Mitchell B (1995) Blood 86 (Suppl 1): 511aGoogle Scholar
  31. 31.
    Kurtzberg J, Keating MJ, Plunkett W, Gandhi V, Gold S, Reese M, Elion G, Mitchell BS (1995) J Clin Oncol 14: 1750Google Scholar
  32. 32.
    Kurtzberg J, Keating MJ, Moore JO, Gandhi S, Blaney W, Gold S, Ernst T, Henske-Downey J, Chang A, Kisor D, Plunkett W, Mitchell B (1996) Blood 88 (Suppl 1): 669aGoogle Scholar
  33. 33.
    Plunkett W, Gandhi V, Nowak B, Du M, Rodriguez CO, Keating MJ (1996) Proc Am Assn Cancer Res 37: 180Google Scholar
  34. 34.
    Gandhi V, Kisor DF, Rodriguez CO, Mitchell BS, Kurtzberg J, Keating MJ, Plunkett W (1996) Blood 88 (Suppl. 1): 670aGoogle Scholar
  35. 35.
    Rodriguez CO Jr, Legha JK, Keating MJ, Estey E, Plunkett W, Gandhi V (1997) Proc Am Assn Cancer Res 38: 101Google Scholar
  36. 36.
    Plunkett W, Liliemark JO, Adams TM, Nowak B, Estey E, Kantarjian H, Keating MJ (1987) Cancer Res 47: 3005–3011PubMedGoogle Scholar
  37. 37.
    Grunewald R, Abbruzzese JL, Tarassoff P, Plunkett W (1991) Cancer Chemother Pharmacol 27: 258–262PubMedCrossRefGoogle Scholar
  38. 38.
    Gandhi V, Estey E, Keating MJ, Plunkett W (1993) Clin Oncol 11: 116–124Google Scholar

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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