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Selective hypersensitivity to granulocyte-macrophage colony-stimulating
factor by juvenile chronic myeloid leukemia hematopoietic progenitors
PD Emanuel, LJ Bates, RP Castleberry, RJ Gualtieri and KS Zuckerman
Department of Medicine, University of Alabama, Birmingham 35294.
Juvenile chronic myelogenous leukemia (JCML) is a good model for the study
of myeloproliferation because JCML hematopoietic progenitor cells grow in
vitro at very low cell densities without the addition of exogenous
stimulus. Previous studies have demonstrated that this proliferation is
dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF), and
that removal of monocytes from the cell population before culture
eliminates this "spontaneous" myeloproliferation, suggesting a paracrine
role of monocyte stimulation. However, subsequent studies have shown that
increased GM-CSF production from the JCML monocytes is not a consistent
finding and therefore not a plausible sole mechanism. In examining
hematopoietic growth factor dose- response curves, both JCML GM and
erythroid nonadherent progenitor cell populations displayed a marked and
selective hypersensitivity to GM- CSF. Responses to interleukin-3 and G-CSF
were identical to control dose-response curves. This is the first
demonstration of a myeloid leukemia in which hypersensitivity to a specific
growth factor appears to be involved in the pathogenesis of the disease.
Volume 77,
Issue 5,
pp. 925-929,
03/01/1991
Copyright © 1991 by The American Society of Hematology
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