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In vitro development of erythroid and megakaryocytic cells from a UT-7
subline, UT-7/GM
N Komatsu, K Kirito, R Shimizu, M Kunitama, M Yamada, M Uchida, M Takatoku, M Eguchi and Y Miura
Department of Medicine, Jichi Medical School, Minamikawachi-machi,
Tochigi-ken, Japan.
UT-7 is a human megakaryoblastic leukemia cell line with absolute
dependence on interleukin-3, granulocyte-macrophage colony-stimulating
factor (GM-CSF), or erythropoietin (EPO) for growth and survival. We
isolated a novel subline, UT-7/GM after long-term culture of UT-7 with
GM-CSF. The hemoglobin concentration and gamma-globin and EPO-receptor mRNA
levels were significantly higher in EPO-treated UT-7/GM cells than in
untreated cells. In contrast, the platelet factor 4 and glycoprotein IIb
mRNA levels were much higher in thrombopoietin (TPO)-treated UT- 7/GM cells
than in untreated cells. Some TPO-treated cells had morphologically mature
megakaryocytic characteristics such as a developed demarcation membrane in
the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM
is a bipotential cell line that can be induced to differentiate into
erythroid and megakaryocytic lineages by EPO and TPO, respectively.
Moreover, a minority of UT-7/GM cells acquired a high hemoglobin
concentration by treatment with TPO, suggesting that TPO in part induced
the erythroid differentiation of the UT-7/GM cells. Interestingly, GM-CSF
inhibited the EPO- or TPO- induced erythroid differentiation and the
TPO-induced megakaryocytic differentiation of UT-7/GM cells. These results
support the hypothesis that cytokines influence the programming of gene
expression required for lineage commitment or differentiation.
Volume 89,
Issue 11,
pp. 4021-4033,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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