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人急性髓细胞白血病中的粒细胞集落刺激因子受体

Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia.

作者信息

Budel L M, Touw I P, Delwel R, Löwenberg B

机构信息

Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.

出版信息

Blood. 1989 Dec;74(8):2668-73.

PMID:2479427
Abstract

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.

摘要

采用放射性标记的重组人粒细胞集落刺激因子(rhG-CSF),研究了粒细胞集落刺激因子(G-CSF)与正常人和人类急性髓系白血病(AML)细胞的结合情况。在所有14例原发性AML中,纯化的原始细胞上均显示出G-CSF的特异性受体。G-CSF受体的平均数量从极低到每个细胞428个受体(平均值)不等。正常粒细胞表面的G-CSF结合位点密度更高(每个细胞703至1296个位点)。G-CSF受体似乎属于单一亲和力类型,AML原始细胞的解离常数(kd)在214至378 pmol/L之间,粒细胞的解离常数在405至648 pmol/L之间。在14例中的12例中,包括那些特异性结合相对较低的病例,G-CSF在体外是原始细胞DNA合成的有效诱导剂;因此,显然相对较少的受体就足以激活AML细胞生长。然而,在两例中,尽管有G-CSF受体,但细胞周期并未因G-CSF而被激活。结果表明,高亲和力的G-CSF受体经常在人类AML的原始细胞上表达,但其存在可能并非细胞对G-CSF增殖反应性的严格指标。

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