Fas receptor (CD95)-mediated apoptosis is induced in leukemic cells entering G1B compartment of the cell cycle.
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.
Komada
Y
Y
Department of Pediatrics, Mie University School of Medicine, Japan.
Zhou
Y W
YW
Zhang
X L
XL
Xue
H L
HL
Sakai
H
H
Tanaka
S
S
Sakatoku
H
H
Sakurai
M
M
D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000032:analysis; D005472:Fluorouracil / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects; D012334:RNA, Neoplasm / Q000032:analysis; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D019014:fas Receptor; D013755:Tetradecanoylphorbol Acetate; D005472:Fluorouracil; D013936:Thymidine