Fas receptor (CD95)-mediated apoptosis in leukemic cells.
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.
Komada
Y
Y
Department of Pediatrics, Mie University School of Medicine, Tsu, Japan.
Sakurai
M
M
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D003602:Cytotoxicity, Immunologic; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D053222:Fas Ligand Protein; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D004273:DNA, Neoplasm; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor