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.