Granulocyte colony‐stimulating factor (G‐CSF) receptors on acute myeloblasts leukaemia cells and their relationship with the proliferative response to G‐CSF in clonogenic assay

Abstract

The number and the affinity of granulocyte colony-stimulating factor (G-CSF) receptors expressed by blast cells in acute myeloblastic leukaemia (AML) were determined using radiolabelled recombinant human G-CSF (rhG-CSF). Eighteen of 20 patients demonstrated specific binding, and Scatchard analysis revealed a single class of high affinity (Kd 15-130 pM) G-CSF receptors on the AML blasts. The number of G-CSF receptors varied from 55 to 1,200 per cell (mean 278). In the remaining two patients, specific binding was not observed. The number of G-CSF receptors did not differ significantly between various AML subtypes, but the mean receptor number was the highest on type M2 blasts. A chemical cross-linking study revealed that the G-CSF receptor has an approximate molecular weight of 140,000. Autoradiography showed heterogeneity of the distribution of G-CSF receptors on the AML blasts obtained from a single patient. The number of colonies stimulated by the addition of rhG-CSF varied from 0 to 566 per dish, and blast colony formation was observed in eight of 20 patients. The population mean of G-CSF receptor number expressed by blasts that formed colonies on stimulation with rhG-CSF was significantly higher than that on blasts which did not form colonies. These results suggest that a proliferative response of AML blasts to G-CSF may be predicted when the blasts express a large number of G-CSF receptors. Accordingly, it may be safer to restrict the clinical use of G-CSF to AML patients who have blasts with a low G-CSF receptor expression and no response to G-CSF in blast colony assay.