Sbarrato T, Horvilleur E, Pöyry T, Hill K, Chaplin L C, Spriggs R V, Stoneley M, Wilson L, Jayne S, Vulliamy T, Beck D, Dokal I, Dyer M J S, Yeomans A M, Packham G, Bushell M, Wagner S D, Willis A E
Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester LE19HN, UK.
The Babraham Institute, Babraham, Cambridge, UK.
Cell Death Dis. 2016 Jun 2;7(6):e2249. doi: 10.1038/cddis.2016.148.
We have used polysome profiling coupled to microarray analysis to examine the translatome of a panel of peripheral blood (PB) B cells isolated from 34 chronic lymphocytic leukaemia (CLL) patients. We have identified a 'ribosome-related' signature in CLL patients with mRNAs encoding for ribosomal proteins and factors that modify ribosomal RNA, e.g. DKC1 (which encodes dyskerin, a pseudouridine synthase), showing reduced polysomal association and decreased expression of the corresponding proteins. Our data suggest a general impact of dyskerin dysregulation on the translational apparatus in CLL and importantly patients with low dyskerin levels have a significantly shorter period of overall survival following treatment. Thus, translational dysregulation of dyskerin could constitute a mechanism by which the CLL PB B cells acquire an aggressive phenotype and thus have a major role in oncogenesis.
我们运用多核糖体谱分析结合微阵列分析，来检测从34例慢性淋巴细胞白血病（CLL）患者分离出的一组外周血（PB）B细胞的翻译组。我们在CLL患者中鉴定出一种“核糖体相关”特征，其中编码核糖体蛋白和修饰核糖体RNA的因子（如DKC1，其编码假尿苷合酶盘状结构域蛋白）的mRNA显示多核糖体结合减少，相应蛋白表达降低。我们的数据表明，盘状结构域蛋白失调对CLL中的翻译装置有普遍影响，重要的是，盘状结构域蛋白水平低的患者治疗后的总生存期明显较短。因此，盘状结构域蛋白的翻译失调可能构成一种机制，通过该机制CLL PB B细胞获得侵袭性表型，从而在肿瘤发生中起主要作用。
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