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Growth regulation of human acute myeloid leukemia: effects of five
recombinant hematopoietic factors in a serum-free culture system
R Delwel, M Salem, C Pellens, L Dorssers, G Wagemaker, S Clark and B Lowenberg
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
The response of human acute myeloid leukemia (AML) cells to the distinct
hematopoietic growth factors (HGFs), ie, recombinant interleukin-3 (IL-3),
granulocyte-macrophage-CSF (GM-CSF), granulocyte- CSF (G-CSF),
macrophage-CSF (M-CSF), and erythropoietin (Epo) was investigated under
well-defined serum-free conditions. Proliferative responses to these
factors, when added separately as well as in combinations, were analyzed in
25 cases of human AML using 3H-thymidine incorporation and colony assays.
The 3H-thymidine uptake data revealed that IL-3, GM-CSF, G-CSF, and M-CSF
were stimulators of AML proliferation in 19, 15, 13, and 4 cases,
respectively. Epo only stimulated DNA synthesis in the cells of the single
erythroleukemia case. GM-CSF stimulation was seen only in IL-3 reactive
cases and GM- CSF, when combined with IL-3, could not further elevate the
DNA synthesis evoked by IL-3 alone. On the other hand, in six cases, G-CSF
enhanced the IL-3- or GM-CSF-stimulated thymidine uptake. These results
suggest that subpopulations of AML cells that are activated by distinct
CSFs (eg, IL-3/GM-CSF-responsive cells and G-CSF-responsive cells) coexist.
The 3H-thymidine incorporation assay was more sensitive for measuring CSF
responses than methylcellulose colony cultures, since activation of DNA
synthesis was more frequently seen than induction of colony formation. DNA
synthesis experiments revealed eight different CSF response patterns among
these 25 cases. CSF phenotyping may be a useful addition to the morphologic
classification of AML, since these patterns directly reflect the ability of
the proliferating subsets of AML cells to respond to the CSFs.
Volume 72,
Issue 6,
pp. 1944-1949,
12/01/1988
Copyright © 1988 by The American Society of Hematology
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