Inhibition of Time-dependent Enhancement of Amino Acid Transport by Leukemic Leukocytes: A Possible Index of the Sensitivity of Cells to Drugs

  • Patrick A. Frengley
  • William A. Peck
  • Marshall A. Lichtman
Conference paper


Leukemic leukocytes increase their rates of alpha aminoisobutyric acid (AIB) accumulation when incubated for prolonged periods in amino acid deficient media. The time-dependent increase was prevented by concurrent exposure of cells to cycloheximide or actinomycin D in vitro. In addition, the increase in AIB uptake was not present in leukemic blasts studied in vitro when the cells were obtained from subjects with acute myeloblastic leukemia who had received antileukemic therapy. Cortisol added to cell suspensions in vitro inhibited the development of time-dependent increases in AIB uptake in lymphoid cells, but accentuated the process slightly in myeloblasts. Cortisol administered to a subject with CLL by infusion reduced the time-dependent increase in AIB uptake by CLL cells subsequently studied in vitro. These data indicate that the time-dependent increase in AIB uptake may be a means of testing the sensitivity of leukemic cells to drugs.

Key Words

Leukemic cells Amino-acid uptake inhibition 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Baran, D.T., Lichtman, M.A., Peck, W.A.: Alpha aminoisobutyric acid transport in human leukemic lymphocytes: In vitro characteristics and inhibition by Cortisol and cycloheximide. J. clin. Invest. 51, 2181, 1972 PubMedCrossRefGoogle Scholar
  2. 2.
    Baran, D.T., Peck, W.A., Frengley, P.A., Lichtman, M.A.: Cortisol induced inhibition of amino acid transport in thymic lymphocytes: Kinetic parameters; relationship to ATP levels and protein synthesis; and specificity. Biochim. biophys. Acta 307, 627, 1973 PubMedCrossRefGoogle Scholar
  3. 3.
    Cline, M.J., Rosenbaum, E.: Prediction of in vivo cytotoxicity of chemotherapeutic agents by their in vitro effects on leukocytes from patients with acute leukemia. Cancer Res. 28, 2516, 1968 PubMedGoogle Scholar
  4. 4.
    Cline, M.J.: In vitro test system for anticancer drugs. (Editorial) New Engl. J. Med. 280, 955, 1969 PubMedCrossRefGoogle Scholar
  5. 5.
    Cline, M.J.: Adrenal steroids in leukemia and lymphoma. Cancer Chem. Rep. 58, 521, 1974 Google Scholar
  6. 6.
    Fallon, H.J., Frei, E. III, Freirich, E.J.: Correlations of biochemical and clinical effects of 6-azuridine in patients with leukemia. Amer. J. Med. 33, 526, 1962 CrossRefGoogle Scholar
  7. 7.
    Frengley, P.A., Lichtman, M.A., Peck, W.A.: Specificity and sensitivity of cortisol-induced changes in alpha aminoisobutyric acid transport in human leukemic small lymphocytes and leukemic myeloblasts. J. clin. Invest. 52, 1518, 1973 CrossRefGoogle Scholar
  8. 8.
    Frengley, P.A., Peck, W.A., Lichtman, M.A.: Accelerated active transport of alpha aminoisobutyric acid by human leukemic leukocytes in an amino acid deficient medium. Exp. Cell Res. 88, 442, 1974 PubMedCrossRefGoogle Scholar
  9. 9.
    Kessel, D., Hall, T.C., Roberts, D.: Modes of uptake of methotrexate by normal and leukemic human leukocytes in vitnxand their relation to drug response. Cancer Res. 28, 564, 1968 PubMedGoogle Scholar
  10. 10.
    Prediction of response to antitumor therapy. National Cancer Institute Monograph No. 34. Hall, T.C. (ed.) Washington, D.C.: U.S. Government Printing Office, 1971 Google Scholar
  11. 11.
    Leinen, J.G., Frengley, P.A., Lichtman, M.A., Wittliff, J.L.: Binding characteristics of triamcinolene acetonide (TAC) receptors in human leukemia. Proc. Amer. Chem. Soc. Northeast Regional Meeting, Abstr. No. 298, Rochester, New York 1973 Google Scholar

Copyright information

© Springer-Verlag Berlin Heildelberg 1975

Authors and Affiliations

  • Patrick A. Frengley
  • William A. Peck
  • Marshall A. Lichtman
    • 1
  1. 1.Departments of Medicine and of Radiation Biology and BiophysicsUniversity of Rochester School of MedicineRochesterUSA

Personalised recommendations