Dührsen U, Knieling G, Hossfeld D K
Abteilung für Onkologie und Hämatologie, Universitätskrankenhaus Eppendorf, Hamburg, Germany.
Int J Cancer. 1995 Mar 3;60(5):652-9. doi: 10.1002/ijc.2910600515.
The recently described PGM-2 leukemia displays a hierarchical structure with bipotential stem cells, B-lymphocyte and macrophage progenitor cells, and post-mitotic end cells. Because the different cell types can easily be identified in vitro by clonal culture assays and simple staining procedures, this leukemia is a useful model for the study of the interactions between different cell compartments in a leukemic clone. Our analysis of the impact of mature leukemic macrophages on the proliferation of stem cells was facilitated by the establishment of long-term cultures producing new stem cells over prolonged periods of time. A prerequisite was the development of an adherent layer of fibroblasts and leukemic macrophages. Enumeration of adherent cells revealed a good correlation between the number of macrophages and the number of stem cells generated, and expansion of the macrophage population by treatment with interleukin 3 (IL-3) resulted in a significant improvement of the culture conditions. Leukemic macrophages were also able to induce the formation of stem-cell colonies in agar culture, suggesting a role for humoral mediators. Antibody neutralization experiments and bioassays identified IL-7 and IL-6 as factors cooperating in the stimulation of stem-cell self-renewal. Feed-back stimulation of leukemic stem cells by mature leukemic cells may also be relevant to human leukemias and have implications for differentiation therapy.
最近描述的PGM - 2白血病表现出一种具有双潜能干细胞、B淋巴细胞和巨噬细胞祖细胞以及有丝分裂后终末细胞的层级结构。由于不同细胞类型可通过克隆培养测定和简单染色程序在体外轻松识别，这种白血病是研究白血病克隆中不同细胞区室间相互作用的有用模型。通过建立能在较长时间内产生新干细胞的长期培养体系，我们对成熟白血病巨噬细胞对干细胞增殖影响的分析得以推进。一个前提条件是形成一层由成纤维细胞和白血病巨噬细胞组成的贴壁层。对贴壁细胞的计数显示巨噬细胞数量与产生的干细胞数量之间存在良好的相关性，并且通过用白细胞介素3（IL - 3）处理使巨噬细胞群体扩增，从而显著改善了培养条件。白血病巨噬细胞还能够在琼脂培养中诱导干细胞集落的形成，提示体液介质发挥了作用。抗体中和实验和生物测定确定IL - 7和IL - 6是协同刺激干细胞自我更新的因子。成熟白血病细胞对白血病干细胞的反馈刺激可能也与人类白血病相关，并对分化治疗有影响。
