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Characterization of granulocyte-macrophage colony-stimulating factor
receptor on the blast cells of acute myeloblastic leukemia
N Onetto-Pothier, N Aumont, A Haman, C Bigras, GG Wong, SC Clark, A De Lean and T Hoang
Clinical Research Institute of Montreal, Quebec, Canada.
Iodinated granulocyte-macrophage colony-stimulating factor (GM-CSF) was
used to document the specific binding of GM-CSF to all acute myeloblastic
leukemia (AML) samples examined in the present study. There was some
heterogeneity in the number of GM-CSF binding sites per cell. To determine
whether the low level of binding to some patient samples may be attributed
to receptor occupancy by an endogenous source of GM-CSF, we devised an acid
wash procedure that could remove surface- bound GM-CSF without affecting
receptor properties. We thus document that GM-CSF specific binding to AML
blasts before or after acid wash was the same, indicating that the observed
heterogeneity in binding is not the result of receptor occupancy by an
endogeneous source of GM- CSF. Saturation analyses are in favor of the
presence of two classes of binding sites on AML blasts: a high-affinity
receptor that binds GM-CSF with a dissociation constant (kd) of 3 to 73
pmol/L and a second class of low-affinity receptor that binds GM-CSF with a
kd of 1 to 10 nmol/L. Binding studies with two established cell lines KG-1,
and IRCM-8 also showed the presence of two classes of binding sites with
high and low affinities. Analysis of GM-CSF titration curves in culture
indicate that the median effective concentration required for stimulation
of blast colony formation (EC50 = 5-36 pmol/L) were in the range of the kd
of the high-affinity binding site, suggesting that this high-affinity
binding site mediates the proliferative response.
Volume 75,
Issue 1,
pp. 59-66,
01/01/1990
Copyright © 1990 by The American Society of Hematology

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