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KMID : 0613820060160050759
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Journal of Life Science
2006 Volume.16 No. 5 p.759 ~ p.766
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Different Responses to Arsenic Trioxide between NB4 and UF-1, Acute Promyelocytic Leukemia Cell Lines
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Kim Hye-Ran
Choi Yoon-Jeong
Ryu Seong-Yeoll
Lee Sang-Hwa
Lee Young-Seok
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Abstract
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Acute promyelocytic leukemia (APL) is a myeloid leukemia caused by over-expression of fusion protein, PML/RAR(α), which was the result of chromosomal translocation and induces the blockage of differentiation of affected promyelocytes. Pharmacological dose of retinoic acid induces the activation of and subsequent degradation of PML/RAR(α) fusion protein, and then APL cells undergo through the normal differentiation pathway. Arsenic trioxide has proved effective in causing remission of acute promyelocytic leukemia by inducing apoptosis of this tumor cells, whereas the heterogeneity of cellular susceptibility to this cytotoxic agent limited its usage on more types of tumors in clinic.
This work showed that arsenic trioxide could induce apoptosis of a panel of acute promyelocytic leukemic cell lines, all-trans-retinoic acid (ATRA) sensitive NB4 cells and ATRA resistant UF-1 cell. They were investigated with regard to the correlation between the inherent or intrinsic cellular level of GSH and the apoptotic susceptibility of the cells to arsenic trioxide. We manifested, in two cell types, the inherently existed difference in intracellular GSH level reactive to the arsenic trioxide, and a positive correlation between the GSH level and their apoptotic sensitivity to arsenic trioxide. And it showed that arsenic trioxide could differentiate promyelocytic cancer cells to the cells possessed of dendritic cell surface markers.
Unravelling the cause of the different susceptibility between leukemic cells and proving that promyelocyte could be differentiated to dendritic cells by arsenic trioxide will help not only to understand the mechanism underlying the complete remission of acute promyelocytic leukemia induced by arsenic trioxide, but also to expand its clinical usage.
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KEYWORD
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Acute promyelocytic leukemia, dendritic cell surface markers, arsenic trioxide
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