Debatin K M, Goldman C K, Waldmann T A, Krammer P H
Oncology/Immunology Section, University Children's Hospital, Heidelberg, Germany.
Blood. 1993 Jun 1;81(11):2972-7.
The 48-Kd cell-surface protein APO-1 is a new member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily. APO-1 is expressed on various cells, including activated T and B cells and some lymphoid and nonlymphoid cell lines. Triggering of APO-1 by the monoclonal antibody anti-APO-1 induces programmed cell death (apoptosis) in APO-1-expressing cells. APO-1 is also present on T-cell lines derived from patients with adult T-cell leukemia (ATL). Therefore, we investigated APO-1 expression and APO-1-mediated induction of apoptosis ex vivo in cells from patients with ATL. Fresh leukemic cells from nine patients with ATL were assayed for APO-1 expression by two-color immunofluorescence. The leukemic cells from all patients strongly expressed APO-1. Incubation of ATL cells with anti-APO-1 in vitro inhibited spontaneous and cytokine-mediated DNA synthesis. Furthermore, DNA isolated from cells treated with anti-APO-1 exhibited polynucleosomal DNA fragmentation (DNA ladder) characteristic for apoptotic cell death. The analysis of APO-1-mediated apoptosis may represent a new approach to the study of growth control in lymphoid malignancies. In addition, induction of apoptosis by administration of anti-APO-1 may represent a new therapeutic approach for aggressive T-cell malignancies such as ATL.
48千道尔顿的细胞表面蛋白APO-1是神经生长因子（NGF）/肿瘤坏死因子（TNF）受体超家族的新成员。APO-1在多种细胞上表达，包括活化的T细胞和B细胞以及一些淋巴细胞和非淋巴细胞系。抗APO-1单克隆抗体触发APO-1可诱导表达APO-1的细胞发生程序性细胞死亡（凋亡）。APO-1也存在于成人T细胞白血病（ATL）患者来源的T细胞系中。因此，我们研究了ATL患者细胞中APO-1的表达以及APO-1介导的体外凋亡诱导情况。通过双色免疫荧光法检测了9例ATL患者新鲜白血病细胞中的APO-1表达。所有患者的白血病细胞均强烈表达APO-1。体外将ATL细胞与抗APO-1孵育可抑制自发的和细胞因子介导的DNA合成。此外，从用抗APO-1处理的细胞中分离的DNA呈现出凋亡细胞死亡特有的多聚核小体DNA片段化（DNA梯带）。对APO-1介导的凋亡的分析可能代表了一种研究淋巴恶性肿瘤生长控制的新方法。此外，给予抗APO-1诱导凋亡可能代表了一种针对侵袭性T细胞恶性肿瘤如ATL的新治疗方法。
