In vitro correlates of clinical response to methotrexate in acute leukaemia and Burkitt's lymphoma
- 1 November 1976
- journal article
- research article
- Published by Springer Nature in British Journal of Cancer
- Vol. 34 (5), 484-492
- https://doi.org/10.1038/bjc.1976.202
Abstract
The response of drug-resistant patients with acute leukaemia and Burkitt's lymphoma to treatment with a 24 h infusion of methotrexate (MTX) followed, in some cases,by cytosine arabinoside was correlated with in vitro measurements of total intracellular MTX, exchangeable intracellular MTX, and suppressibility of deoxyuridine (UdR) incorporation in isolated marrow blast cells at extracellular MTX concentrations of 10(-8)M, 10(-7)M, 10(-6)M and 10(-5)M. Total intracellular MTX levels and exchangeable intracellular MTX levels were not significantly different in responding or non-responding patients at any MTX concentration, but increased four-fold for every ten-fold concentration increment studied. Extracellular MTX levels in excess of 10(-7)M appeared necessary to allow accumulation of exchangeable intracellular MTX. UdR incorporation at 10(-6)M and 10(-5)M differed significantly between responding and non-responding patients, with responders having less than 20% of control values and non-responders having greater than 40% of control values. Further, increasing the extracellular MTX concentration from 10(-6)M to 10(-5)M produced no significant decrease in UdR incorporation in either group. The therapeutic implications of this apparent threshold are discussed.Keywords
This publication has 13 references indexed in Scilit:
- Biochemical determinants of 5-fluorouracil response in vivo. The role of deoxyuridylate pool expansion.JCI Insight, 1975
- Alteration of methotrexate uptake in human leukemia cells by other agents.1975
- Clinical correlates of in vitro effect of methotrexate on acute leukemia blasts.1974
- Concentration of Immature and Mature Granulocytes from Normal Human Bone MarrowExperimental Biology and Medicine, 1974
- The mechanism of action of methotrexate. I. Interaction with a low-affinity intracellular site required for maximum inhibition of deoxyribonucleic acid synthesis in L-cell mouse fibroblasts.1974
- Transport of Methotrexate into Normal Haemopoietic Cells and into Leukaemic Cells and its Effects on DNA SynthesisBritish Journal of Haematology, 1973
- Cell kinetics and chemotherapy in acute leukemia.1972
- Treatment of leukemia with large doses of methotrexate and folinic acid: clinical-biochemical correlatesJCI Insight, 1969
- Carrier-mediated Transport of the Folic Acid Analogue, Methotrexate, in the L1210 Leukemia CellJournal of Biological Chemistry, 1968
- TECHNIQUES FOR STUDY OF RESISTANCE TO FOLIC ACID ANTAGONISTS.1964