Persisting production of out-of-cycle blasts during methotrexate therapy in acute leukaemia.
Kinetics of the blast populations in two cases of acute lymphoblastic leukaemia during treatment with methotrexate have been studied in vivo. Beside a striking cytocidal effect on blasts arrested in the S phase and a synchronization and a slowing of those in the G2 phase, the most important finding was the persistence of a flux of drug-affected cells from the proliferation of the non-proliferating compartment. Some of these non-proliferating cells were able to re-enter subsequently the mitotic cycle. This fact can explain why a cell-cycle-specific drug fails to eradicate completely acute leukaemic cells in man.
D000328:Adult; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007945:Leukemia, Lymphoid / Q000097:blood / Q000188:drug therapy*; D007958:Leukocyte Count; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D008938:Mitosis / Q000187:drug effects
D008727:Methotrexate