Interleukin-3 and granulocyte-monocyte colony-stimulating factor receptors
on human acute myelocytic leukemia cells and relationship to the
proliferative response
LM Budel, IP Touw, R Delwel, SC Clark and B Lowenberg
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Interleukin-3 (IL-3) and granulocyte-monocyte-colony-stimulating factor
(GM-CSF) stimulate proliferation of human acute myeloid leukemia (AML) in
vitro, although patterns of response among clinical cases are diverse.
Whether regulatory abnormalities related to growth factor responses in
human AML may establish the outgrowth of the neoplasm is unclear. We
determined receptor numbers and affinity for IL-3 and GM- CSF on human AML
cells using human recombinant IL-3 (rIL-3) and GM-CSF (rGM-CSF). In 13 of
15 cases of primary AML high-affinity (kd 26 to 414 pmol/L) receptors for
IL-3 were demonstrable on the cells. The average numbers of IL-3 receptors
ranged from 21 to 145 receptors per cell. Normal WBCs showed IL-3 receptors
on their surface at similar densities. IL-3 receptor positivity often
correlated with GM-CSF receptor positivity of AML; GM-CSF receptors were
demonstrated on the cells of 11 of 15 cases, although average numbers of
GM-CSF receptors were ten times greater. The in vitro response of the cells
to exogenous IL-3 or GM-CSF was examined by measuring thymidine uptake.
Because IL-3 and GM-CSF were potent inducers of DNA synthesis in vitro,
apparently relatively few receptors are required to permit activation of
growth. These experiments did not provide evidence for overexpression or
increased receptor sensitivity as an explanation for AML growth. In a
minority of cases, however, the cells were unable to respond to IL-3 (four
of 15 cases) or GM-CSF (four of 15 cases) despite normal receptor
availability on the cell surface.
Volume 74,
Issue 2,
pp. 565-571,
08/01/1989
Copyright © 1989 by The American Society of Hematology
