Motoji T, Watanabe M, Uzumaki H, Kusaka M, Fukamachi H, Shimosaka A, Oshimi K, Mizoguchi H
Department of Medicine, Tokyo Women's Medical College, Japan.
Br J Haematol. 1991 Jan;77(1):54-9. doi: 10.1111/j.1365-2141.1991.tb07948.x.
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.
利用放射性标记的重组人粒细胞集落刺激因子(rhG-CSF)测定急性髓细胞白血病(AML)原始细胞表达的粒细胞集落刺激因子(G-CSF)受体的数量和亲和力。20例患者中有18例表现出特异性结合,Scatchard分析显示AML原始细胞上存在一类高亲和力(解离常数Kd为15 - 130 pM)的G-CSF受体。每个细胞的G-CSF受体数量在55至1200个之间(平均为278个)。其余2例患者未观察到特异性结合。不同AML亚型之间G-CSF受体数量无显著差异,但M2型原始细胞上的平均受体数量最高。化学交联研究表明,G-CSF受体的分子量约为140,000。放射自显影显示,从一名患者获得的AML原始细胞上G-CSF受体的分布存在异质性。添加rhG-CSF后刺激形成的集落数量每培养皿从0至566个不等,20例患者中有8例观察到原始细胞集落形成。用rhG-CSF刺激后形成集落的原始细胞表达的G-CSF受体数量的总体平均值显著高于未形成集落的原始细胞。这些结果表明,当AML原始细胞表达大量G-CSF受体时,可能预测其对G-CSF的增殖反应。因此,将G-CSF的临床应用限制于那些原始细胞G-CSF受体表达低且在原始细胞集落测定中对G-CSF无反应的AML患者可能更安全。