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首页> 外文期刊>Cell biology international. >Effects of epigenetic-based anti-cancer drugs in leukaemia and multiple myeloma cells.
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Effects of epigenetic-based anti-cancer drugs in leukaemia and multiple myeloma cells.

机译：基于表观遗传学的抗癌药在白血病和多发性骨髓瘤细胞中的作用。

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摘要

Here, we focus on epigenetic changes in leukaemia and MM (multiple myeloma) cells. We show how the histone signature, DNA methylation and levels of select tumour-suppressor proteins can be affected by inhibitors of HDACs (histone deacetylases) and Dnmts (DNA methyltransferases). Both inhibitors, TSA (trichostatin A) and 5-AZA (5-azacytidine), have the ability to change the histone signature in a tumour-specific manner. In MM cells, we observed changes in H3K4 methylation, while in leukaemia cells, H3K9 methylation was especially affected by select inhibitors. Compared with normal peripheral blood lymphocytes, tumour cell samples were characterized by increased H3K9 acetylation, increased H3K4me2, H3K9me2 and HP1alpha (heterochromatin protein 1alpha) levels and specific changes were also observed for DNA methylation. Additionally, we showed that the tumour suppressor pRb1 (retinoblastoma protein) is more sensitive to epigenetic-based anti-cancer stimuli than p53. We have found significant decrease in the levels of pRb1 and p53 in both myeloma and leukaemia cells after HDAC inhibition.
机译：在这里，我们关注白血病和MM（多发性骨髓瘤）细胞的表观遗传学变化。我们展示了HDACs（组蛋白脱乙酰基酶）和Dnmts（DNA甲基转移酶）的抑制剂如何影响组蛋白签名，DNA甲基化和所选肿瘤抑制蛋白的水平。两种抑制剂，TSA（trichostatin A）和5-AZA（5-azacytidine），都具有以肿瘤特异性方式改变组蛋白特征的能力。在MM细胞中，我们观察到H3K4甲基化的变化，而在白血病细胞中，H3K9甲基化特别受选择抑制剂的影响。与正常的外周血淋巴细胞相比，肿瘤细胞样品的特征在于增加的H3K9乙酰化，增加的H3K4me2，H3K9me2和HP1alpha（异染色质蛋白1alpha）水平，并且还观察到DNA甲基化的特异性变化。此外，我们表明，肿瘤抑制因子pRb1（视网膜母细胞瘤蛋白）对基于表观遗传学的抗癌刺激比p53更为敏感。我们发现HDAC抑制后，骨髓瘤和白血病细胞中pRb1和p53的水平显着降低。

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