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Kit ligand in synergy with interleukin-3 amplifies the erythropoietin-
independent, globin-synthesizing progeny of normal human burst-forming
units-erythroid in suspension cultures: physiologic implications
T Papayannopoulou, M Brice and CA Blau
Department of Medicine, University of Washington, Seattle 98195.
Although the proliferative effects of hematopoietic cytokines on erythroid
progenitors are well known, parameters that influence the initiation of
expression of specialized or lineage-restricted genes are not clear. We
have studied the acquisition of erythroid-differentiative features from
enriched populations of human early erythroid progenitors (burst-forming
unit-erythroid [BFUe]) in suspension culture and the influence of several
cytokines on this process. In suspension cultures containing no
erythropoietin (Epo), we have found that kit ligand (KL) in synergy with
interleukin-3 not only increases the proliferation of cells and of
progenitors but also consistently amplifies a population of cells that
contain globin within 1 week. Our experiments suggest that neither
extraneously provided nor endogenously produced Epo is critical for the
generation of globin-synthesizing cells. Globin- producing cells generated
mostly from late BFUe or pre-CFUe with a CD34- /EP-1+ phenotype in this
system do not all express a well-coordinated erythroid program accompanied
by heme or glycophorin A expression and most die maintaining an immature
state. Therefore, conditions that are responsible for initiation of globin
expression in these cells are not sufficient to carry them to terminal
maturation. The data point to an expanded target cell population for KL, as
they suggest an influence of KL on survival and/or amplification of late
erythroid cells previously thought to be influenced only by Epo. Our
results in aggregate are of relevance to the physiology of normal
erythropoiesis and the role of Epo and KL in the initial stages of
lineage-restricted gene expression. In addition, they provide insight into
the understanding of anemia in W and Steel mutants in which expansion of
the late erythroid progenitor pool, normally dependent on the synergistic
action of KL and Epo, is curtailed.
Volume 81,
Issue 2,
pp. 299-310,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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