Anti-Fas IgM monoclonal antibody enhances apoptosis induced by low-dose cytosine arabinoside.
BACKGROUND
Although low-dose cytosine arabinoside (LD-Ara-C) therapy has been accepted as an effective treatment for patients with acute non-lymphocytic leukemia (ANLL) transformed from myelodysplastic syndromes or elderly patients with ANLL, the anti-leukemic mechanism remains to be resolved. Recently, the potential role of the Fas/Fas ligand system in chemotherapeutic drug-induced apoptosis has been studied. In the present study the relationship between the anti-leukemic effect of LD-Ara-C and the Fas/Fas ligand system was examined.


METHODS
The human myeloid leukemia cell line HL60 was treated with LD-Ara-C in combination with anti-Fas IgM MoAb, and apoptosis in the treated cells was estimated by morphological observation, DNA electrophoresis and flow cytometry. Simultaneously, changes in Fas antigen expression on cells treated with LD-Ara-C were investigated.


RESULTS
Only limited apoptosis was observed following treatment with LD-Ara-C alone or anti-Fas MoAb alone; however, a synergistic increase in apoptosis was observed by treatment with the MoAb in combination with pretreatment with LD-Ara-C. LD-Ara-C induced a slight but consistent increase in the expression of Fas antigen on the treated cells. Moreover, the expression of Fas antigen was enhanced by repeated administration of LD-Ara-C.


CONCLUSIONS
These findings suggest the possible involvement of the Fas/Fas ligand system in the anti-leukemic effect of LD-Ara-C therapy.
Nakamura
S
S
Third Department of Medicine, School of Medicine, Faculty of Medicine, Kanazawa University, Japan.
Takeshima
M
M
Nakamura
Y
Y
Ohtake
S
S
Matsuda
T
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003561:Cytarabine / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D019014:fas Receptor / Q000032:analysis / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D007075:Immunoglobulin M; D019014:fas Receptor; D003561:Cytarabine