Leukemic cell death induced by antithymocyte globulin.
We studied the cytotoxic effects of antithymocyte globulin (ATG) in leukemic cells obtained from five patients with acute T lymphoblastic leukemia or precursor T lymphoblastic leukemia. ATG by itself killed leukemic cells in a dose-dependent manner. Simultaneous incubation with human AB or baby rabbit serum resulted in increased cytolysis of leukemic cells. These results suggested the presence of both direct and complement-mediated cytolysis. We also examined apoptotic cell death using Annexin-V. Cell incubation with ATG increased Annexin-V binding significantly compared with horse IgG (50.3+/-7.6% versus 95.7+/-1.8%, p = or < 0.0001). However, ATG did not induce apparent DNA fragmentation in a human T-ALL cell line. Neither anti-Fas MoAb (ZB4) nor a broad caspase inhibitor (z-VAD FMK) prevented this increase in Annexin-V binding. These results suggest that ATG induces leukemic cell death in a Fas/Fas-ligand- and caspase-independent manner.
Yoshimi
Ayami
A
Department of Pediatrics/Developmental Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Ito
Masahumi
M
Kojima
Seiji
S
D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D006736:Horses; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000473:pathology*
D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents