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Monoclonal antibodies to the human CSF-1 receptor (c-fms proto-oncogene
product) detect epitopes on normal mononuclear phagocytes and on human
myeloid leukemic blast cells
RA Ashmun, AT Look, WM Roberts, MF Roussel, S Seremetis, M Ohtsuka and CJ Sherr
Department of Tumor Cell Biology, St. Jude Children's Research Hospital,
Memphis, TN 38101.
The first monoclonal antibodies (MoAbs) to epitopes in the extracellular
domain of the human c-fms proto-oncogene product (receptor for the
macrophage colony stimulating factor, CSF-1) were used with flow cytometric
techniques to study receptor expression on normal human peripheral blood
monocytes, bone marrow cells, and leukemic blasts. On normal cells CSF-1
receptors were restricted in their expression to cells of the mononuclear
phagocyte lineage. CSF-1 receptors were detected on leukemic blasts from 15
(30%) of 50 children with acute myeloid leukemia, compared with four (15%)
of 26 adults. By contrast, detectable CSF-1 receptors were uniformly absent
on blasts from 19 children with acute lymphoblastic leukemia. CSF-1
receptors on normal monocytes and myeloid leukemia cells could be induced
to downmodulate by incubation with either human recombinant CSF-1 or
phorbol esters, confirming that the receptors had functional ligand-
binding sites and responded to transmodulation by inducers of protein
kinase C. The numbers of receptors per cell and the percentage of positive
cases were highest for leukemic blasts with cytochemical and morphological
features of monocytes. However, CSF-1 receptors were also detected on a
subset of leukemic blast cells with features of granulocytic
differentiation (FAB subtypes M1 through M3). Southern blotting analyses of
DNA from 47 cases of acute myeloid leukemia demonstrated no rearrangements
within the 32 kb of genomic sequences that contain CSF-1 receptor coding
exons or in the 50 kb upstream of the first coding exon. Analysis of the
upstream region of the c-fms locus revealed that sequences representing the
terminal 112 untranslated nucleotides of c-fms mRNA map 26 kb 5' to the
first coding exon, suggesting that at least one c-fms promoter is separated
from the receptor coding sequences by a very long intron. Whereas
expression of the CSF-1 receptor in myeloid leukemic blasts is not
restricted to cells with monocytic characteristics, the apparently aberrant
pattern of receptor synthesis in a subset of cases with granulocytic
features appears not to be due to chromosomal rearrangements within 50 kb
upstream of sequences encoding the receptor.
Volume 73,
Issue 3,
pp. 827-837,
02/15/1989
Copyright © 1989 by The American Society of Hematology
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