Anticancer Effect of Arsenic Trioxide in Acute Promyelocytic Leukemia

PURPOSE: Acute promyelocytic leukemia (APL or AML, M3) represents an unique model for cancer research in terms of biological and clinical features. Since 1988, it has been widely confirmed that all-trans retinoic acid (ATRA) can induce complete clinical remission in over 85% of APL patients by a differentiation process, with PML-RARalpha protein possibly being the direct target of ATRA. However, ATRA treatment has two clinical limitations, namely, retinoic acid syndrome and retinoic resistance. Recently, it has been shown that arsenic trioxide used in some traditional Chinese remedy is very effective in retinoic resistant APL treatment. We tried to observe arsenic effect on cell lines and APL patient cells. MEHTODS: We investigated arsenic trioxide-induced apoptosis on APL, HL60, K562, KPH1 cell lines through MTT assay, DNA fragmentation assay and morphologic features. RESULTS: In MTT assay, cell survival rate decreased as the concentration of arsenic trioxide increased. In DNA fragmentation assay with HL60 cell line, DNA fragmentation was more frequent in high concentrations of arsenic trioxide than in low concentrations. During arsenic trioxide treatment, the morphologic change in bone marrow cells of APL patient, included nuclear differentiation and dark cytoplasmic granule during arsenic trioxide treatment. Serum arsenic reached peak level at 4hr after injection. We experienced a case of a 9-year-old male with APL who had relapsed after cessation of retinoic acid treatment. The patient successfully achieved remission following arsenic trioxide treatment without bone marrow depression and exacerbating bleeding diathesis. CONCLUSION: Arsenic trioxide can be used effectively to treat APL patients by inducing apoptosis and partial differentiation in tumor cells. The precise cellular and molecular mechanisms of its therapeutic effects remain to be determined.

A Case of Relapsed Acute Promyleocytic Leukemia Induced Remission with Arsenic Trioxide(As2O3)

Acute promyelocytic leukemia(APL) is a unique entity in the spectrum of acute myelogenous leukemia. It has several characteristic features, including distinctive morphology, chromosomal translocation, t(15:17), disseminated intravascular coagulation and effect on retinoic acid. Retinoic acid which is a derivative of vitamin A induces differentation of APL cells in vitro and in vivo, but its cessation induces relapse of APL. Arsenic trioxide(AszOz) can induce clinical remission in patients with APL, including those who have relapsed after retinonic acid treatment. We report a case of a 9-year-old male with APL who had relapsed after cessation of retinoic acid treatment. The patient successfully achieved remission following treatment with AsO. Arsenic trioxide treatment would be an effective and relatively safe drug in childhood APL patients refractory to retinoic acid.