Variable susceptibility to apoptosis induced by calcium ionophore in hybridomas between HL-60 promyelocytic and CEM T-lymphoblastic leukemia cell lines: relationship to constitutive Mg(2+)-dependent endonuclease.

We recently reported that treatment with calcium ionophore, A23187, induces apoptosis in human myelogenous leukemia cells but causes necrotic cell death in T-lymphoblastic leukemia cells. To better understand the underlying mechanisms of such different modes of cell death, we established hybridomas between HL-60 promyelocytic and CEM T-lymphoblastic leukemia cells. The resulting hybridomas were divided into three groups in terms of their susceptibility to apoptosis following exposure to 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, growth inhibition after 72 h of incubation and an initial rise in intracellular free calcium concentrations induced by A23187 were similar in the three groups. Expression of Ca(2+)-independent/Mg(2+)-dependent endonuclease, 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-induced apoptosis. Thus, this endonuclease may play, at least in part, an important role in the induction of apoptosis in leukemia cell lines. Analysis of hybridomas between apoptosis-sensitive and apoptosis-resistant cells is useful in the elucidation of genetic factors which regulate cell death.