THE INDUCTION OF APOPTOSIS AND CELL-CYCLE ARREST BY ARSENIC TRIOXIDE IN LYMPHOID NEOPLASMS

Arsenic trioxide (As2O3) has recently been shown to induce complete re mission in acute promyelocytic leukemia (APL). As2O3 reportedly has do se-dependent dual effects on APL cells, triggering apoptosis at relati vely high concentrations and inducing differentiation at lower concent rations. However, its effect is still controversial for other AML cell s and hematological neoplasms. We studied the in vitro effect of As2O3 on lymphoid lineage cells: lymphoma cell lines, NOL-3, Raji and Daudi , a myeloma cell line, NOP-1, normal peripheral blood lymphocytes (PBL ), non-Hodgkin's lymphoma (NHL) cells and chronic lymphocytic leukemia (CLL) cells, and compared it with the effect on APL cell line, NB4, a s well as other myeloid cell lines, HL-60 and NKM-1. As2O3 at a concen tration of 1 mu mol/l markedly inhibited both proliferation and Viabil ity of NB4, NOP-1, NOL-3 and NKM-1 cells, but it reduced only viabilit y in normal PBL, CLL cells and NHL cells. As2O3 induced apoptosis and down-regulated bcl-2 expression in NB4, NOP-1 and NKM-1. cells. On the other hand, in HL-60, Raji and Daudi cells, 1 mu mol/l As2O3 inhibite d only the proliferation weakly, and neither induced apoptosis nor dow n-regulated bcl-2 expression, but arrested only cell cycle at G(1) pha se. As2O3 at a low concentration of 0.1 mu mol/l had no effect on prol iferation and viability of these cells except for NB4. These results s howed that As2O3 exerted variable and definite effects on lymphoid cel ls and indicated that As2O3 might be clinically useful in lymphoid neo plasms such as malignant lymphoma and CLL.