Histone deacetylase inhibitor but not arsenic trioxide differentiates acute promyelocytic leukaemia cells with t(11;17) in combination with all-trans retinoic acid.
作者： Kunio Kitamura , Shinetsu Hoshi , Mitsuru Koike , Hitoshi Kiyoi , Hidehiko Saito
DOI: 10.1046/J.1365-2141.2000.01933.X
关键词: Trichostatin A 、 Retinoid 、 Histone deacetylase inhibitor 、 Arsenic trioxide 、 Cancer research 、 Leukemia 、 Histone deacetylase 、 Biochemistry 、 Tretinoin 、 Biology 、 Retinoic acid
摘要: Acute promyelocytic leukaemia (APL) with t(11;17)/PLZF-RARalpha responds poorly to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), in contrast APL t(15;17)/PML-RARalpha. Molecular studies have shown that histone deacetylase (HDAC) recruited by PLZF-RARalpha is associated the ATRA resistance. Here, we analysed vitro differentiation of cells t(11;17) using ATRA, As203, granulocyte colony-stimulating factor (G-CSF), HDAC inhibitor trichostatin A (TSA), or combinations these. Although 1 microM which stimulated t(15;17), was insufficient induce differentiation, 3 induced terminal into granulocytes. As203 alone combination neither nor apoptosis. However, TSA had a potent differentiating effect, although little effect. The G-CSF did not differentiation. These results indicate need higher concentration than those t(15;17) differentiate suggest promising enhancer t(11;17).
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