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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 550-559
The Glucocorticoid Receptor Cooperates With the Erythropoietin Receptor
and c-Kit to Enhance and Sustain Proliferation of Erythroid Progenitors
In Vitro
Marieke von Lindern,
Wolfgang Zauner,
Georg Mellitzer,
Peter Steinlein,
Gerhard Fritsch,
Klaus Huber,
Bob Löwenberg, and
Hartmut Beug
From the Institute of Hematology, Erasmus University, Rotterdam, The
Netherlands; the Institute of Molecular Pathology, Vienna, Austria; the
Children's Cancer Research Institute, St. Anna Kinderspital, Vienna,
Austria; and the Department of Laboratory Medicine, Donauspital
SMZ-Ost, Vienna, Austria.
Although erythropoietin (Epo) is essential for the production of
mature red blood cells, the cooperation with other factors is required
for a proper balance between progenitor proliferation and
differentiation. In avian erythroid progenitors, steroid hormones cooperate with tyrosine kinase receptors to induce renewal of erythroid
progenitors. We examined the role of corticosteroids in the in vitro
expansion of primary human erythroid cells in liquid cultures and
colony assays. Dexamethasone (Dex), a synthetic glucocorticoid hormone,
cooperated with Epo and stem cell factor to induce erythroid
progenitors to undergo 15 to 22 cell divisions, corresponding to a
105- to 106-fold amplification of erythroid
cells. Dex acted directly on erythroid progenitors and maintained the
colony-forming capacity of the progenitor cells expanded in liquid
cultures. The hormone delayed terminal differentiation into
erythrocytes, which was assayed by morphology, hemoglobin accumulation,
and the expression of genes characteristic for immature cells.
Sustained proliferation of erythroid progenitors could be induced
equally well from purified erythroid burst-forming units (BFU-E), from
CD34+ blast cells, and from bone marrow depleted from
CD34+ cells.
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