Komada Y, Sakurai M
Department of Pediatrics, Mie University School of Medicine, Tsu, Japan.
Leuk Lymphoma. 1997 Mar;25(1-2):9-21. doi: 10.3109/10428199709042492.
Binding of Fas ligand (FasL) or an agonistic anti-Fas receptor (Fas/CD95) antibody induces apoptosis in Fas-bearing target cells. The involvement of Fas/FasL pathway has been investigated in human acute myelogenous leukemia (AML) cells. Fas/CD95 is expressed on a majority of AML cells, although the intensity of expression is variable. The cross-linking with anti-Fas antibody can induce apoptotic cell death in certain cases of AML. When DNA synthesis and cell cycle progression are enhanced by growth-promoting cytokines, such as interleukin-3 and granulocyte-macrophage colony-stimulating factor, Fas-insensitive AML cells acquire cellular susceptibility toward Fas-mediated apoptosis. Cell cycle analysis reveals that Fas-mediated apoptotic signals can be transduced into cells in G1B compartment and G1A-->G1B transition might support the induction of Fas-mediated apoptosis. In addition, Fas-mediated apoptotic cell death of AML cells is also induced by interleukin-2-activated T cells expressing functional FasL on their surfaces. Activated T cells express a large amount of FasL mRNA, compared with freshly isolated T cells. The Fas/FasL pathway seems to be the major mechanism of T cell-mediated apoptosis in AML cells, although alternative mechanisms can also be operative. The induction of apoptosis in Fas/FasL system might be a novel and effective approach for leukemia immunotherapy.
Fas配体（FasL）或抗Fas受体激动性抗体（Fas/CD95）的结合可诱导表达Fas的靶细胞发生凋亡。Fas/FasL途径在人类急性髓性白血病（AML）细胞中的作用已得到研究。大多数AML细胞表达Fas/CD95，尽管表达强度存在差异。在某些AML病例中，抗Fas抗体交联可诱导凋亡性细胞死亡。当生长促进细胞因子如白细胞介素-3和粒细胞-巨噬细胞集落刺激因子增强DNA合成和细胞周期进程时，Fas不敏感的AML细胞获得对Fas介导凋亡的细胞敏感性。细胞周期分析显示，Fas介导的凋亡信号可在G1B期转导至细胞，G1A向G1B的转变可能支持Fas介导凋亡的诱导。此外，AML细胞的Fas介导凋亡性细胞死亡也可由表面表达功能性FasL的白细胞介素-2激活的T细胞诱导。与新鲜分离的T细胞相比，活化的T细胞表达大量的FasL mRNA。Fas/FasL途径似乎是AML细胞中T细胞介导凋亡的主要机制，尽管也可能存在其他机制。Fas/FasL系统中凋亡的诱导可能是白血病免疫治疗的一种新的有效方法。
