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Establishment and characterization of the thrombopoietin-dependent
megakaryocytic cell line, UT-7/TPO
N Komatsu, M Kunitama, M Yamada, T Hagiwara, T Kato, H Miyazaki, M Eguchi, M Yamamoto and Y Miura
Division of Hematology, Department of Medicine, Jichi Medical School,
Tochigi, Japan.
UT-7 is a human megakaryoblastic leukemia cell line with absolute
dependence on interleukin-3, granulocyte-macrophage colony-stimulating
factor, or erythropoietin (EPO) for growth and survival. We investigated
the effect of thrombopoietin (TPO), the ligand for the receptor encoded by
c-mpl proto-oncogene, on the proliferation and differentiation of UT-7 and
its sublines. We found that UT-7/GM, which is a subline of UT-7, but
neither UT-7 nor UT-7/EPO, can proliferate in response to TPO. The subline,
UT-7/TPO, was established from UT-7/GM by culture at lower concentrations
of TPO. UT-7/TPO cells had morphologically mature megakaryocytic
characteristics such as developed demarcation membrane in the cytoplasm and
multinucleated appearance. This was also confirmed by the high expression
of platelet factor-4 and glycoprotein IIb at the mRNA levels and by the
high level of DNA content. UT-7/TPO can be maintained by TPO alone, with a
doubling time of 24 hours in log growth phase. In the absence of TPO, the
majority of the cells died within a few days. Thus, UT-7/TPO has an
absolute dependence on TPO for growth and survival and has mature
megakaryocytic features. The mRNA for c-mpl was detected in UT-7/TPO and,
to a lesser degree, in UT-7/GM. The mRNA level of NF- E2 p45, reported to
be an erythroid-specific transcription factor, was upregulated in UT-7/TPO,
whereas it was down-regulated in the erythroid subline, UT-7/EPO. There
were no significant differences in GATA-1 and GATA-2 mRNA levels among UT-7
and its sublines. Not only EPO but also TPO induced the tyrosine
phosphorylation of JAK2 tyrosine kinase and STAT5-related protein. These
findings indicate that UT-7/TPO would be a useful model with which to
analyze the gene regulation of megakaryocytic maturation- associated
proteins and to study the specific actions of TPO.
Volume 87,
Issue 11,
pp. 4552-4560,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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