Komada Y, Zhou Y W, Zhang X L, Xue H L, Sakai H, Tanaka S, Sakatoku H, Sakurai M
Department of Pediatrics, Mie University School of Medicine, Japan.
Blood. 1995 Nov 15;86(10):3848-60.
Apoptotic cell death induced by cross-linking Fas receptor (FasR/CD95) has been investigated in human acute myelogenous leukemia (AML) cells. FasR-mediated growth inhibition and DNA fragmentation could be induced in certain cases of AML. Interestingly, when DNA synthesis and G1 -> S transition in the cell cycle were enhanced by interleukin-3 or granulocyte-macrophage colony-stimulating factor, Fas-insensitive blast cells acquired cellular susceptibility toward FasR-mediated growth inhibition. To further evaluate an association between the Fas-R-mediated action and a specific phase of the cell cycle, a FasR+ leukemic cell line, MML-1, was established from a patient with AML. The morphologic feature of dying cells and DNA fragmentation indicated that FasR cross-linking induced apoptotic cell death in MML-1 cells. Cell cycle arrest in G1A phase with the treatment of phorbol 12-myristate 13-acetate or thymidine rendered MML-1 cells resistant to FasR-mediated apoptosis without downregulation of surface FasR expression. However, S-phase arrest with 5-fluorouracil could neither enhance nor inhibit FasR-mediated apoptosis. Simultaneous DNA/RNA quantification analysis revealed the selective loss of cells in G1B compartment, accompanied by the increase of apoptotic nuclei in sub-G1 fraction. These findings suggested that FasR-mediated apoptotic signals could be transduced into cells in G1B compartment and G1A -> G1B transition might augment the induction of FasR-mediated apoptosis.
在人类急性髓性白血病（AML）细胞中，已对交联Fas受体（FasR/CD95）诱导的凋亡性细胞死亡进行了研究。在某些AML病例中可诱导FasR介导的生长抑制和DNA片段化。有趣的是，当白细胞介素-3或粒细胞-巨噬细胞集落刺激因子增强细胞周期中的DNA合成和G1期向S期转变时，Fas不敏感的原始细胞获得了对FasR介导的生长抑制的细胞敏感性。为了进一步评估Fas-R介导的作用与细胞周期特定阶段之间的关联，从一名AML患者中建立了FasR+白血病细胞系MML-1。死亡细胞的形态特征和DNA片段化表明，FasR交联在MML-1细胞中诱导了凋亡性细胞死亡。用佛波醇12-肉豆蔻酸酯13-乙酸酯或胸苷处理使MML-1细胞在G1A期发生细胞周期阻滞，从而使其对FasR介导的凋亡具有抗性，而表面FasR表达并未下调。然而，5-氟尿嘧啶导致的S期阻滞既不能增强也不能抑制FasR介导的凋亡。同时进行的DNA/RNA定量分析显示，G1B区室中的细胞选择性丢失，同时亚G1部分中凋亡细胞核增加。这些发现表明，FasR介导的凋亡信号可在G1B区室中传导至细胞，并且G1A期向G1B期的转变可能会增强FasR介导的凋亡诱导作用。
