Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia.
The binding of granulocyte colony-stimulating factor (G-CSF) to normal and human acute myeloid leukemia (AML) cells was investigated with radiolabeled recombinant human G-CSF (rhG-CSF). In all 14 cases of primary AML specific receptors for G-CSF were demonstrated on purified blast cells. The average numbers of G-CSF receptors ranged from very low to 428 receptors per cell (mean). Normal granulocytes showed G-CSF binding sites on their surface at higher densities (703 to 1,296 sites per cell). G-CSF receptors appeared to be of a single affinity type with a dissociation constant (kd) ranging between 214 and 378 pmol/L for AML blasts and 405 to 648 pmol/L for granulocytes. 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; therefore, apparently relatively few receptors are required to permit activation of AML cell growth. However, in two cases cell cycling was not activated in response to G-CSF despite G-CSF receptor availability. The results show that G-CSF receptors of high affinity are frequently expressed on the blasts of human AML, but their presence may not be a strict indicator of the proliferative responsiveness of the cells to G-CSF.
Budel
L M
LM
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Touw
I P
IP
Delwel
R
R
Löwenberg
B
B
D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000378:metabolism* / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D011956:Receptors, Cell Surface; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor