IL-3, GM-CSF and G-CSF stimulate proliferation of human acute myeloid leukemia in vitro, but patterns of response among clinical cases are diverse. As described in Chapters 2 and 3, numbers and affinity of IL-3, GM-CSF and G-CSF receptors on cells of patients with AML were assessed and correlated with the proliferative response of the cells to IL-3, GM-CSF and G-CSF. In 13 of 15 cases of primary AML high affinity receptors for IL-3 were demonstrable on the cells. The average numbers of IL-3 receptors ranged from 21-145 receptors per cell. Normal white blood cells showed IL-3 receptors on their surface at similar densities. IL-3 receptor positivity often correlated with GM-CSF receptor positivity of AML, GMCSF receptors were demonstrated on the cells of 11 of 15 cases although average numbers of GM-CSF receptors were 10 times greater. The binding of G-CSF to normal and human AML cells was investigated in a series of 14 cases of primary AML. In all 14 cases specific receptors for G-CSF were demonstrated on purified blast cells. The average numbers of G-CSF receptors ranged from very low (specific binding scarcely detectable) to 428 receptors per cell. Normal granulocytes showed G-CSF binding sites on their surface at higher densities (703 to 1,296 sites/cell). GCSF receptors appeared of a single affinity type with a dissociation constant (Kct) ranging between 214 to 378 pM for AML blasts and 405 to 648 pM for normal peripheral blood granulocytes. The in vitro response of the cells to exogenous IL-3, GM-CSF or G-CSF was examined by measuring thymidine uptake. IL-3 and GM-CSF were potent inducers of DNA synthesis in vitro. In 12 of 14 cases including those with relatively low specific binding, G-CSF was a potent inducer of DNA synthesis of blasts in vitro; apparently relatively few receptors permit activation of AML cell growth. In a minority of cases however, the cells were unable to respond to IL-3 (4 of 15 cases), GM-CSF (4 of 15 cases) or G-CSF (2 of 14 cases) in spite of normal receptor availability on the cell surface. The inability of the cells to respond to stimulation might be caused by the inability of the receptors to transduce a secondary signal into the cells. The results from these experiments taken together did not provide evidence for overexpression or gross changes in receptor affinity as an explanation for AML growth

Additional Metadata
Keywords Myyloid Leukemia, Receptors
Promotor Löwenberg, B. (Bob)
Publisher Erasmus University Rotterdam
Persistent URL hdl.handle.net/1765/37784
Citation
Budel, L.M.. (1993, December 23). GM-CSF, IL-3 and G-CSF receptors on acute myeloid leukemia cells : function, regulation of expression, and ligand binding characteristics. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/37784