Journal of the Korean Pediatric Society 2000;43(3):327-334.
Published online March 15, 2000.
Anticancer Effect of Arsenic Trioxide in Acute Promyelocytic Leukemia
Ki Young Song1, Jin Hye Park1, Yoon Jung Cho1, Won Ki Baek2, Ki Young Kwon3, Heung Sik Kim1, Chin Moo Kang1
1Department of Pediatrics, School of Medicine, Keimyung University, Taegu, Korea
2Department of Microbiology, School of Medicine, Keimyung University, Taegu, Korea
3Department of Pediatrics Internal Medicine, School of Medicine, Keimyung University, Taegu, Korea
급성 전골수성 백혈병에 대한 Arsenic trioxide(As2O3)의 항암 작용
송기영1, 박진휘1, 조윤정1, 백원기2, 권기영3, 김흥식1, 강진무1
1계명대학교 의과대학 소아과학교실
2계명대학교 의과대학 미생물학교실
3계명대학교 의과대학 내과학교실
Abstract
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-RARα 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.
Methods
: 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.
Key Words: Arsenic trioxide, Acute promyelocytic leukemia(APL), Childhood


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