Akashi K, Harada M, Shibuya T, Eto T, Takamatsu Y, Teshima T, Niho Y
First Department of Internal Medicine, Faculty of Medicine, Fukuoka, Japan.
Blood. 1991 Jul 1;78(1):197-204.
We studied the effects of interleukin-4 (IL-4) and IL-6 on the growth of leukemic blasts from 40 patients with acute myelogenous leukemia (AML). Patients were selected on the basis of negativity for a series of B-cell antigens including CD10 and CD19. Twenty-one cases were CD34-positive (CD34+) (greater than 15% of blasts) and the remaining 19 were CD34-negative (CD34-) (less than 3% of blasts). IL-4 alone (100 U/ml) could stimulate either DNA synthesis (with greater than 2.0 stimulation index) or leukemic blast colony formation in 24 of 40 AML patients. In the presence of other growth factors, IL-4 showed divergent effects on IL-3-, granulocyte-macrophage colony-stimulating factor-, granulocyte colony-stimulating factor-, or erythropoietin-dependent colony formation. These effects of IL-4 were observed in both CD34+ and CD34- AML cases. IL-6 (100 U/mL) alone could not stimulate DNA synthesis and blast colony formation except for one CD34+ case. On the other hand, IL-6 showed synergistic effects on IL-3- and IL-4-dependent blast colony formation in 10 of 12 and 7 of 9 CD34+ AML cases, respectively. Among CD34- AML cases, such synergism was seen only in 1 of 12 cases for IL-3-dependent colony formation and in 3 of 7 cases for IL-4-dependent colony formation. The divergent effect of IL-4 and the synergistic effect of IL-6 were also observed in purified CD34+ leukemic blast populations, indicating that these phenomena are not mediated by accessory cells. The present study suggests that IL-4, alone or in combination with other growth factors, has divergent effects on the growth of AML progenitors irrespective of the CD34 expression, and that IL-6 acts synergistically with IL-3 or IL-4 on the growth of leukemic progenitors preferentially in CD34+ AML.
我们研究了白细胞介素-4（IL-4）和白细胞介素-6对40例急性髓性白血病（AML）患者白血病原始细胞生长的影响。患者的选择基于一系列B细胞抗原（包括CD10和CD19）呈阴性。21例为CD34阳性（CD34+）（原始细胞大于15%），其余19例为CD34阴性（CD34-）（原始细胞小于3%）。单独使用IL-4（100 U/ml）可刺激40例AML患者中的24例出现DNA合成（刺激指数大于2.0）或白血病原始细胞集落形成。在存在其他生长因子的情况下，IL-4对IL-3、粒细胞-巨噬细胞集落刺激因子、粒细胞集落刺激因子或促红细胞生成素依赖的集落形成表现出不同的作用。在CD34+和CD34- AML病例中均观察到了IL-4的这些作用。单独使用IL-6（100 U/mL）除1例CD34+病例外，不能刺激DNA合成和原始细胞集落形成。另一方面，IL-6分别在12例CD34+ AML病例中的10例和9例中的7例中对IL-3和IL-4依赖的原始细胞集落形成表现出协同作用。在CD34- AML病例中，这种协同作用仅在12例中的1例出现于IL-3依赖的集落形成，在7例中的3例出现于IL-4依赖的集落形成。在纯化的CD34+白血病原始细胞群体中也观察到了IL-4的不同作用和IL-6的协同作用，表明这些现象不是由辅助细胞介导的。本研究表明，IL-4单独或与其他生长因子联合使用时，无论CD34表达如何，对AML祖细胞的生长均有不同作用，并且IL-6在CD34+ AML中优先与IL-3或IL-4协同作用于白血病祖细胞的生长。
