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Blasts from patients with acute myelogenous leukemia express functional
receptors for stem cell factor
VC Broudy, FO Smith, N Lin, KM Zsebo, J Egrie and ID Bernstein
Department of Medicine, University of Washington, Seattle 98195.
Stem cell factor (SCF) acts in concert with lineage-specific growth factors
to stimulate the growth of hematopoietic colonies. To determine if
neoplastic human hematopoietic cells would also respond to SCF, we cultured
marrow mononuclear cells from 20 patients with newly diagnosed acute
myelogenous leukemia (AML) and two normal donors with SCF, interleukin 3
(IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or
combinations of growth factors in semisolid medium, and assessed colony
growth. SCF receptors (c-kit receptors) were quantitated by equilibrium
binding studies with 125I-SCF, and binding parameters were estimated using
the ligand program. The cellular distribution of c-kit receptors was
determined by autoradiography. Our results show that SCF alone or in
combination with IL-3 or GM-CSF increased both the number and size of
colonies in 10 of the patients. Receptors for SCF were identified on the
blasts from all 20 AML patients. The number of receptors ranged from 600 to
29,000 per cell. In the majority of patients, both high- and low-affinity
binding sites were identified. Neither the number of receptors per cell nor
the finding of one or two classes of receptors correlated with growth
response to SCF. Autoradiographic analysis of 125I-SCF binding to normal
marrow mononuclear cells revealed grains associated with blasts and
megakaryocytes. Grain counts on blasts from 10 AML patients and on normal
marrow blasts suggested that high-affinity c-kit receptor expression on AML
blasts is lower than or similar to that of normal blasts. These results
identify c-kit receptors on human AML blasts, and indicate that SCF acts
synergistically with IL-3 or GM-CSF to stimulate colony growth from the
marrow cells of a portion of patients with AML.
Volume 80,
Issue 1,
pp. 60-67,
07/01/1992
Copyright © 1992 by The American Society of Hematology
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