Re-entry of resting leukaemic blood cells into proliferation in human acute leukaemia during diffusion chamber culture

Abstract

From 17 patients with different forms of acute leukaemia, mononuclear blood cells were cultured in diffusion chambers (DC) implanted intraperitoneally into pre-irradiated mice. In 14 patients, growth of blast cells could be observed during the culture period of up to 21 days. To question whether this growth of blast cells was due only to proliferation of the initially proliferating fraction or whether a re-entry of resting leukaemic cells into proliferation was involved, various 3H-thymidine (3H-TdR) labelling studies were carried out. The absolute increase of blast cells in EC showed no correlation with the fraction of leukaemic blast cells in DNA-synthesis in the implanted cell suspension as measured by 3H-TdR labelling in vitro. Furthermore, in 2 patients where the kinetic behaviour of initially labelled leukaemic blast cells was followed during DC culture, the increase in total blast cells could only be attributed to a small extent to proliferation of those cells initially in the cell cycle. Lastly, "in vivo" labelling during the culture period showed that in one case 25% and in another case 60% of the blast cells in DC were proliferating. The conclusion is that, owing to the stimulation of the diffusion chamber milieu and possibly also due to removal of an in vivo inhibition, in most cases of acute leukaemia resting leukaemic blast cells can apparently re-enter the active cell cycle. This has relevance for an understanding of the self-maintenance of the leukaemic cell population and may also be a reason for relapse of leukaemia after the usual cytostatic drug treatment which affects mainly the proliferating leukaemic cells.