Reilly I A, Kozlowski R, Russell N H
University Department of Haematology, City Hospital, Nottingham.
Br J Haematol. 1989 Jul;72(3):363-9. doi: 10.1111/j.1365-2141.1989.tb07717.x.
The ability of blast cells to grow autonomously and to produce autostimulatory growth factors has been investigated in 25 consecutive patients with AML. An autostimulatory index (ASI) was calculated (no. of colonies without CSF divided by no. of colonies with CSF) and patients classified into four groups: Group 1 (n = 3): non-growers; Group 2 (n = 4): CSF-dependent (ASI less than 0.1); Group 3 (n = 11): partially autonomous (ASI 0.1-0.8); and Group 4 (n = 7): fully autonomous/CSF-unresponsive (ASI greater than 0.8). In Group 3 patients colony formation and DNA synthesis were significantly (P less than 0.01) augmented by CSFs but at high cell concentrations became CSF-independent. Blast cell-conditioned medium (BCCM) from these patients exhibited potent autostimulatory activity, increasing DNA synthesis by less than or equal to 5-fold, and also stimulated CSF-dependent homologous blasts by less than or equal to 20-fold. In 5/5 this activity was neutralized by anti-GM-CSF, which also inhibited autonomous proliferation of their blast cells. Group 4 blasts also secreted GM-CSF but their BCCM possessed no autostimulatory activity, and anti GM-CSF failed to inhibit their autonomous growth. No membrane-associated CSF activity was found, however purified cytosolic fractions stimulated proliferation of CSF-dependent homologous blasts, consistent with production and secretion of CSF which is present in active form in the cytosol but does not autostimulate via membrane receptors. These results suggest that autocrine mechanisms are important in regulating blast cell proliferation, but that the mechanisms are heterogeneous.
对25例急性髓系白血病（AML）患者连续进行研究，以探讨原始细胞自主生长及产生自身刺激生长因子的能力。计算自身刺激指数（ASI）（无集落刺激因子时的集落数除以有集落刺激因子时的集落数），并将患者分为四组：第1组（n = 3）：不生长组；第2组（n = 4）：集落刺激因子依赖组（ASI小于0.1）；第3组（n = 11）：部分自主组（ASI为0.1 - 0.8）；第4组（n = 7）：完全自主/对集落刺激因子无反应组（ASI大于0.8）。第3组患者的集落形成和DNA合成在集落刺激因子作用下显著增强（P小于0.01），但在高细胞浓度时变得不依赖集落刺激因子。这些患者的原始细胞条件培养基（BCCM）表现出强大的自身刺激活性，使DNA合成增加小于或等于5倍，并且也使集落刺激因子依赖的同源原始细胞刺激增加小于或等于20倍。在5例患者中，这种活性被抗GM - CSF中和，抗GM - CSF也抑制了其原始细胞的自主增殖。第4组原始细胞也分泌GM - CSF，但其BCCM没有自身刺激活性，抗GM - CSF也未能抑制其自主生长。未发现膜相关的集落刺激因子活性，然而纯化的胞质部分刺激了集落刺激因子依赖的同源原始细胞的增殖，这与集落刺激因子的产生和分泌一致，集落刺激因子以活性形式存在于胞质溶胶中，但不通过膜受体进行自身刺激。这些结果表明自分泌机制在调节原始细胞增殖中很重要，但机制是异质性的。
