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Granulocyte-macrophage colony-stimulating factor and erythropoietin act
competitively to induce two different programs of differentiation in the
human pluripotent cell line UT-7
O Hermine, P Mayeux, M Titeux, MT Mitjavila, N Casadevall, J Guichard, N Komatsu, T Suda, Y Miura and W Vainchenker
INSERM U.91, Hopital Henri Mondor, Creteil, France.
The UT-7 cell line was established from a patient with a megakaryoblastic
leukemia (Komatsu et al, Cancer Res 51: 341, 1991). Its proliferation is
strictly dependent on the presence of hematopoietic growth factors
including erythropoietin (Epo), granulocyte-macrophage colony-stimulating
factor (GM-CSF), and interleukin-3 (IL-3). We investigated the
differentiation capacities of this cell line under the action of several
growth factors, using immunomarkers, flow cytometry, and ultrastructural
techniques. In the presence of GM-CSF and IL-3, eosinophil and basophil
promyelocytes were detected, as well as a few cells with erythroid and
megakaryocytic (MK) differentiation features. In contrast, Epo induced a
marked erythroid differentiation with an increase of glycophorin A
expression, accompanied by a few hemoglobinized cells. Differentiation
induced by the growth factors took 24 to 48 hours to begin, and increased
with cell passages to a plateau at 2 weeks of culture. However, this was
not only due to a cell selection because the differential effects of Epo
and GM-CSF were observed from a single cell clone and the phenotype could
be reversed by opposite growth factors, even after a long period of
culture. We subsequently investigated the phenotype of UT-7 in the presence
of combinations of Epo, IL-3, and GM-CSF, and showed that GM- CSF and IL-3
act predominantly over Epo. This effect was mediated by a rapid
downmodulation of Epo receptors by GM-CSF at messenger RNA and binding
sites levels, without a change in receptor affinities. On the other hand,
Epo had no effect on number and affinity of GM-CSF receptors. This study
shows that UT-7 is a growth factor-dependent pluripotent cell line in which
commitment may be directed by a hierarchical action of growth factors
through an early and rapid transmodulation of growth factor receptors.
Volume 80,
Issue 12,
pp. 3060-3069,
12/15/1992
Copyright © 1992 by The American Society of Hematology
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