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Epigenomic repression by APL oncoprotein

机译:APL癌蛋白抑制表观基因组

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摘要

In acute promyelocytic leukemia (APL), a t(15;17) translocation leads to the production of PML-RARa, the fusion oncoprotein responsible for the vast majority of APL cases. Expression of PML-RARa leads to transcriptional repression of RARa target genes and a differentiation block at the promyelocytic stage, but also to a unique responsiveness to treatment with all-trans retinoic acid (ATRA).In this issue of Blood, Hoemme and colleagues present a comprehensive study using chromatin precipitation (ChIP)-chip as well as microarrays to analyze changes that occur with induced expression of PML-RARa in a promonocytic cell line. The authors used different antibodies to correlate PML-RARa binding to gene promoters with epigenetic modifications, including histone acetylation and methylation
机译:在急性早幼粒细胞白血病(APL)中,t(15; 17)易位导致PML-RARa的产生,PML-RARa是导致大多数APL病例的融合癌蛋白。 PML-RARa的表达导致RARa目标基因的转录抑制和早幼粒细胞分化的阻滞,但也导致对全反式维甲酸(ATRA)治疗的独特反应。一项使用染色质沉淀(ChIP)芯片以及微阵列的综合研究,分析了原代单核细胞系中PML-RARa诱导表达引起的变化。作者使用了不同的抗体将PML-RARa与基因启动子的结合与表观遗传修饰相关联,包括组蛋白乙酰化和甲基化

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