Quantitative analysis of histone H3 and H4 post-translational modifications in doxorubicin-resistant leukemia cells
Quantitative analysis of histone H3 and H4 post-translational modifications in doxorubicin-resistant leukemia cells
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DOI：
10.1002/bmc.3608
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发表时间：
2016-04-01
影响因子：
1.8
通讯作者：
Wang, Hao
中科院分区：
文献类型：
--
作者：
Liu, Tao;Guo, Qingcheng;Wang, Hao
通过组蛋白修饰的染色质的表观遗传重塑已经被广泛地牵涉到癌细胞的耐药性。然而，表观遗传机制是否有助于白血病阿霉素耐药性尚未仔细研究。使用基于LC-MS的稳定且灵敏的工作流程，我们定量比较了急性白血病细胞系HL 60及其多柔比星耐药衍生物HL 60/ADR以及慢性白血病细胞系K562及其多柔比星耐药衍生物K562/ADR中组蛋白H3和H4的甲基化和乙酰化程度。我们发现H3 K9甲基化、H3 K14、H3 K18和H3 K23乙酰化以及潜在的H4 K20甲基化水平的增加与两种细胞中的耐药性相关。我们的研究结果表明，阿霉素耐药的急性和慢性白血病细胞系可能有一个共同的表观遗传机制，涉及转录激活和沉默的组合。版权所有（c）2015约翰威利父子有限公司
The epigenetic remodeling of chromatin through histone modifications has been widely implicated in drug resistance of cancer cells. However, whether epigenetic mechanisms contribute specifically to doxorubicin resistance in leukemia has not been carefully examined. Using a stable and sensitive workflow based on LC-MS, we quantitatively compared the extents of methylation and acetylation of histone H3 and H4 in acute leukemia cell line HL60 and its doxorubicin-resistant derivative, HL60/ADR, as well as the chronic leukemia cell line K562 and its doxorubicin-resistant derivative, K562/ADR. We found that increased levels of H3K9 methylation, H3K14, H3K18 and H3K23 acetylation, and potentially H4K20 methylation, are associated with drug resistance in both cells. Our results demonstrated that the doxorubicin-resistant acute and chronic leukemia cell lines may share a common epigenetic mechanism that involves a combination of transcriptional activation and silencing. Copyright (c) 2015 John Wiley & Sons, Ltd.