Maturation of human acute myeloid leukaemia in vitro: the response to five recombinant haematopoietic factors in a serum-free system.
The abilities of human recombinant IL-3, GM-CSF, G-CSF, M-CSF and Epo to induce maturation in human AML cells in vitro were investigated using cell specimens from 25 AML patients. The experiments were carried out under exactly defined serum-free culture conditions. In the absence of CSFs, monocytic and/or granulocytic maturation was detected in 14/25 cases. IL-3, GM-CSF, G-CSF and M-CSF elevated the proportions of monocyte/macrophages in 3/25, 2/25, 1/25 and 6/25 cases respectively, and increased the percentages of mature granulocytes in 2/25, 1/25, 1/25 and 0/25 cases, and if so only to a limited extent (values below 50%). The 3H-thymidine (3H-TdR) uptake studies revealed that IL-3, GM-CSF, G-CSF and M-CSF were efficient stimulators of DNA synthesis of AML cells in 19, 15, 13 and four of those cases, respectively. Thus, although the cells in most cases responded to CSFs by activation of DNA synthesis, they were unable to give rise to terminally differentiated stages. Provision of CSFs in combination was more frequently effective in enhancing maturation and also increased the magnitude of maturation response. Monocytic versus granulocytic maturation of AML cells after culture did not correlate with the FAB cytology nor with the type of CSF presented; but generally granulocytic maturation was an infrequent phenomenon. Epo stimulated erythroid differentiation and DNA synthesis only in the case of erythroleukaemia, but it had no effect on the cells of 10 other AML cases. Extrapolation of these in vitro findings would suggest that CSFs would have a limited therapeutic utility to induce AML cell maturation in vivo and that hazards of stimulating blast cell proliferation with these factors may be anticipated.
Salem
M
M
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Delwel
R
R
Mahmoud
L A
LA
Clark
S
S
Elbasousy
E M
EM
Löwenberg
B
B
D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages; D009000:Monocytes; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D004921:Erythropoietin; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor