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表观基因组分析在真性红细胞增多症和原发性血小板增多症中显示出低水平的异常 DNA 甲基化。

Epigenomic profiling in polycythaemia vera and essential thrombocythaemia shows low levels of aberrant DNA methylation.

机构信息

Servicio de Hematología, Hospital Universitario 12 de Octubre, Avenida Córdoba s/n, Madrid, Spain.

出版信息

J Clin Pathol. 2011 Nov;64(11):1010-3. doi: 10.1136/jclinpath-2011-200175. Epub 2011 Aug 6.

Abstract

AIMS

The purpose of this study was to compare the DNA-methylation signature in classic chronic Philadelphia negative myeloproliferative neoplasms (MPN), polycythaemia vera (PV) and essential thrombocythaemia (ET), in order to obtain a global insight into DNA-methylation changes associated with these malignancies.

METHODS

Thirty-five MPN samples from 11 ET JAK2 V617F, 12 ET JAK2 wild type (WT) and 12 PV JAK2 V617F patients as well as 12 from healthy donors were analysed. DNA samples extracted from whole peripheral blood were hybridised to the 'HumanMethylation27 DNA Analysis BeadChip.'

RESULTS

All groups showed a very homogeneous methylation pattern. Only the ZNF577 gene showed a differential methylation profile between PV JAK2 V617F positive and controls. This aberrant methylation was correlated with a differential gene expression of ZNF577. No aberrant hypermethylation was found in the SOCS-1 and SOCS-3 genes.

CONCLUSIONS

According to our results, an aberrant methylation pattern does not seem to play a crucial role in MPN pathogenesis; nor does it justify phenotypical differences between PV and ET.

摘要

目的

本研究旨在比较经典慢性费城阴性骨髓增殖性肿瘤(MPN)、真性红细胞增多症(PV)和特发性血小板增多症(ET)中的 DNA 甲基化特征,以期全面了解与这些恶性肿瘤相关的 DNA 甲基化变化。

方法

分析了 11 例 ET JAK2 V617F、12 例 ET JAK2 野生型(WT)和 12 例 PV JAK2 V617F 患者以及 12 例健康供体的 35 例 MPN 样本。从全外周血中提取的 DNA 样本与“HumanMethylation27 DNA Analysis BeadChip”杂交。

结果

所有组均显示出非常均匀的甲基化模式。只有 ZNF577 基因在 PV JAK2 V617F 阳性和对照组之间显示出不同的甲基化谱。这种异常甲基化与 ZNF577 的差异基因表达相关。SOCS-1 和 SOCS-3 基因未发现异常高甲基化。

结论

根据我们的结果,异常甲基化模式似乎在 MPN 发病机制中不起关键作用;也不能说明 PV 和 ET 之间的表型差异。

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