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Erythropoietin-induced activation of STAT5 is impaired in the
myelodysplastic syndrome
LH Hoefsloot, MP van Amelsvoort, LC Broeders, DC van der Plas, K van Lom, H Hoogerbrugge, IP Touw and B Lowenberg
Institute of Hematology, Erasmus University Rotterdam, Department of
Hematology, Dijkzigt Hospital, Rotterdam, The Netherlands.
Patients with myelodysplastic syndrome (MDS) have ineffective in vivo and
in vitro erythropoiesis, characterized by an impaired response to
erythropoietin (Epo). We examined proliferation and maturation of MDS
marrow cells in response to Epo in more detail. Epo-dependent DNA synthesis
as well as induction of GATA-1 binding activity in marrow cells from 15 MDS
cases were severely reduced as compared with normal bone marrow (NBM).
Additionally, the appearance of morphologically identifiable erythroid
cells was decreased in MDS cell cultures. These data indicate that both the
Epo-dependent proliferation as well as the differentiation induction by Epo
is suppressed. To study more upstream events of the Epo signal transduction
route we investigated activation of the signal transducer and activator of
transcription (STAT) 5. In all 15 MDS samples tested, STAT5 activation was
absent or greatly suppressed in response to Epo. In contrast, interleukin-3
induced a normal STAT5 response in MDS cells. Further, in MDS the subset of
CD71+ BM cells that is phenotypically similar to Epo-responsive cells in
normal marrow, was present. We conclude that the Epo response in MDS is
disturbed at an early point in the Epo-receptor (EpoR) signal transduction
pathway.
Volume 89,
Issue 5,
pp. 1690-1700,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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