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 = <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.