Methotrexate Metabolism by Bone Marrow Cells from Patients with Leukemia

  • V. Michael Whitehead
  • David S. Rosenblatt
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 163)


Bone marrow cells from children with leukemia in remission and lymphoblasts and myeloblasts from children with early and late-stage leukemia all accumulated methotrexate during short-term culture and converted it to poly-γ-glutamyl derivatives. This metabolism was time and dose-dependent. Leukemia cells from two patients with chronic myelocytic leukemia also synthesized methotrexate polygluta-mates. Patients varied one from another in the quantity of total non-exchangeable methotrexate and methotrexate polyglutamates present in cells, but highest levels of each of these were seen in late acute lymphoblastic leukemia and in acute myeloblastic leukemia.

Co-incubation of leukemic cells with both methotrexate and a ten-fold excess of folinic acid decreased accumulation and poly-glutamylation of methotrexate to the same extent as chieved by reducing methotrexate concentration ten-fold. Co-incubation with methotrexate and a ten-fold excess of vincristine did not increase total cell methotrexate and methotrexate polyglutamates in leukemic cells in culture. Such an increase had been anticipated from earlier studiese with other cells. Indeed, levels of methotrexate and its derivatives were modestly reduced.


Folinic Acid Kemic Cell Methotrexate Polyglutamates Remission Bone Marrow Normal Human Bone Marrow Cell 


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Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • V. Michael Whitehead
    • 1
  • David S. Rosenblatt
    • 1
  1. 1.The Penny Cole Haematology Research Laboratory and the Medical Research Council Genetics GroupThe McGill University-Montreal Children’s Hospital Research Institute and the McGill Cancer CenterMontrealCanada

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