VARIABLE SUSCEPTIBILITY TO APOPTOSIS INDUCED BY CALCIUM IONOPHORE IN HYBRIDOMAS BETWEEN HL-60 PROMYELOCYTIC AND CEM T-LYMPHOBLASTIC LEUKEMIA-CELL LINES - RELATIONSHIP TO CONSTITUTIVE MG2-DEPENDENT ENDONUCLEASE()

We recently reported that treatment with calcium ionophore, A23187, in duces apoptosis in human myelogenous leukemia cells but causes necroti c cell death in T-lymphoblastic leukemia cells. To better understand t he underlying mechanisms of such different modes of cell death, we est ablished hybridomas between HL-60 promyelocytic and CEM T-lymphoblasti c leukemia cells. The resulting hybridomas were divided into three gro ups in terms of their susceptibility to apoptosis following exposure t o A23187: (1) hybridomas highly sensitive to apoptosis, (2) hybridomas with intermediate sensitivity to apoptosis which occurs later and to a lesser extent, and (3) hybridomas resistant to apoptosis. However, g rowth inhibition after 72 h of incubation and an initial rise in intra cellular free calcium concentrations induced by A23187 were similar in the three groups. Expression of Ca2+-independent/Mg2+-dependent endon uclease, which had an optimal pH of 7.5-8.5 and was inhibited by Zn2+, was correlated with the susceptibility of the hybridomas to A23187-in duced apoptosis. Thus, this endonuclease may play, at least in part, a n important role in the induction of apoptosis in leukemia cell lines. Analysis of hybridomas between apoptosis-sensitive and apoptosis-resi stant cells is useful in the elucidation of genetic factors which regu late cell death. (C) 1994 Academic Press, Inc.