Murohashi I, Tohda S, Suzuki T, Nagata K, Yamashita Y, Nara N
First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Blood. 1989 Jul;74(1):35-41.
Autocrine growth mechanisms of leukemic blast progenitors in acute myeloblastic leukemia (AML) were investigated. Colony formation of leukemic blast progenitors was observed in 14 of 14 patients tested when purified blast cell fraction depleted of both T cells and monocytes was plated in methylcellulose without any colony-stimulating factor (CSF). However, there existed a minimal cell density required to initiate blast progenitor growth with marked patient-to-patient variation. To clarify the role of cell density on the spontaneous growth of blast progenitors, we tested whether leukemic cells produced and secreted some stimulatory humoral factor(s). Production of colony-stimulating activity (CSA) by blast cells was observed in 17 of 18 patients tested. Following further depletion of monocytes, the CSA levels decreased markedly in 14 patients, indicating that blast cells with monocytoid differentiation were responsible for CSA production. We also confirmed granulocyte colony-stimulating factor (G-CSF) and/or granulocyte macrophage-colony-stimulating factor (GM-CSF) production by leukemic blasts using specific immunologic assays. When leukemic cells were divided into nonadherent nonphagocytic cell fraction and adherent cell fraction, only nonadherent nonphagocytic cells showed clonogenecity and adherent blast cells lacked the colony-forming capacity. The results indicate that there are at least two blast cell subpopulations in AML: one is proliferating subpopulation with self-renewal capacity and the other is supporting subpopulation with functions such as CSF production. The quite intimate relationship between these two blast cell subpopulations in AML may play an important role on the growth of leukemic blast progenitors in vitro.
对急性髓性白血病（AML）中白血病母细胞祖细胞的自分泌生长机制进行了研究。当将去除了T细胞和单核细胞的纯化母细胞部分接种于不含任何集落刺激因子（CSF）的甲基纤维素中时，在14例受试患者中的14例观察到了白血病母细胞祖细胞的集落形成。然而，启动母细胞祖细胞生长存在一个最小细胞密度，且患者之间存在显著差异。为了阐明细胞密度对母细胞祖细胞自发生长的作用，我们测试了白血病细胞是否产生并分泌了一些刺激性体液因子。在18例受试患者中的17例观察到母细胞产生集落刺激活性（CSA）。进一步去除单核细胞后，14例患者的CSA水平显著下降，表明具有单核样分化的母细胞负责CSA的产生。我们还使用特异性免疫测定法证实了白血病母细胞产生粒细胞集落刺激因子（G-CSF）和/或粒细胞巨噬细胞集落刺激因子（GM-CSF）。当白血病细胞分为非贴壁非吞噬细胞部分和贴壁细胞部分时，只有非贴壁非吞噬细胞显示出克隆形成能力，而贴壁母细胞缺乏集落形成能力。结果表明，AML中至少存在两个母细胞亚群：一个是具有自我更新能力的增殖亚群，另一个是具有如CSF产生等功能的支持亚群。AML中这两个母细胞亚群之间非常密切的关系可能在白血病母细胞祖细胞的体外生长中起重要作用。
