Upregulation of B220 expression correlates with sensitivity to arsenic trioxide (As2O3)-induced cell death in different leukemic T-cell lines (132.11)

Abstract

Abstract As2O3 kills a variety of leukemia cells, but with different efficacy. Although cellular redox status is considered essential for As2O3 sensitivity, we show here that murine and human leukemic T-cell lines display dramatic differences in As2O3 sensitivity independently of their GSH content and O2− production. Unexpectedly, As2O3 differently upregulated expression of phosphatase B220 on these T cells in dose-dependent manner. Since we previously reported that As2O3 selectively eliminates pathogenic B220+ T cells in autoimmune MRL/lpr mice (Bobé et al, BLOOD, 2006, 108:30967), we have studied the possible correlation between B220 expression and As2O3-induced T-cell death in leukemic T-cell lines. In the presence of As2O3, we found low (HPB-ALL), intermediate (Jurkat) and high (EL-4, BW5147) levels of both B220 expression and cell death. Ca2+ ionophore A23187 also upregulated B220 expression and cell death, but with opposite efficiencies in the T-cell lines compared to As2O3. A23187 only upregulated the T-cell activation marker CD69 before B220 expression and cell death, suggesting that it kills by an activation-induced cell death mechanism. In L1210 cells, we found constitutive B220 expression. L1210 cells were the most resistant to cell death among As2O3-treated T-cell lines whereas they were the most sensitive to A23187. As2O3 and A23187 probably trigger different signaling pathways through B220 leading to T-cell death, suggesting a checkpoint role for B220 in death pathways.