MicroRNA expression profile in granulocytes from primary myelofibrosis patients
MicroRNA expression profile in granulocytes from primary myelofibrosis patients
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DOI：
10.1016/j.exphein.2007.08.020
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发表时间：
2007-11-01
影响因子：
2.6
通讯作者：
Vannucchi, Alessandro M.
中科院分区：
文献类型：
--
作者：
Guglielmelli, Paola;Tozzi, Lorenzo;Vannucchi, Alessandro M.
客观的。在从原发性骨髓纤维化 (PMF) 患者分离的粒细胞中进行了 microRNA (miRNA) 的表达谱分析，目的是与正常受试者或真性红细胞增多症 (PV) 或原发性血小板增多症 (ET) 患者相比，识别异常表达的 miRNA。 患者和方法。使用茎环引物逆转录和 TaqMan 定量实时聚合酶链反应，使用来自 PMF 患者（野生型或等位基因负荷 >51% 的 JAK2(617V>F) F 突变体）和对照受试者的混合粒细胞评估 156 种成熟 miRNA 的表达。然后在额外的对照和 PMF 样品以及 PV 或 ET 粒细胞上验证差异表达的 miRNA。结果。 PMF 粒细胞中 miRNA 表达全面下调；与正常样本相比，128 个 miRNA 中有 60 个显示出差异表达。根据统计上不同的表达水平选择的 12 个 miRNA 最终得到验证。在 PMF 粒细胞中，与对照和 PV 或 ET 样本相比，miR-31、-150 和 -95 的水平显着降低，而 miR-190 的水平显着升高；另一方面，与对照组相比，PMF、PV 或 ET 患者的 miR-34a、-342、-326、-105、-149 和 -147 也同样减少。 miR-182 和-183 表达增加与 JAK2(617V>F) 等位基因负荷相关。计算机预测的三个推定靶基因（DTR、HMGA2 和 MYB）显示 PMF 粒细胞中的表达失调，与调节 miRNA 的表达水平相关。结论。明确的 miRNA 谱可将 PMF 粒细胞与正常受试者的粒细胞区分开来，部分地也与 PV 或 ET 患者的粒细胞区分开来。 (C) 2007 ISEH - 血液学和干细胞学会。由爱思唯尔公司出版
Objective. Expression profiling of microRNA (miRNA) was performed in granulocytes isolated from patients with primary myelofibrosis (PMF), with the aim of identifying abnormally expressed miRNAs in comparison with normal subjects or patients with polycythemia vera (PV) or essential thrombocythemia (ET).Patients and Methods. Using stem loop-primed reverse transcription and TaqMan quantitative real-time polymerase chain reaction, the expression of 156 mature miRNAs was evaluated using pooled granulocytes from PMF patients, either wild-type or JAK2(617V>F) F mutant with >51% allele burden, and control subjects. Differentially expressed miRNAs were then validated on additional control and PMF samples, and also on PV or ET granulocytes.Results. There was a global downregulation of miRNA expression in PMF granulocytes; 60 miRNAs, of 128 called present, displayed differential expression compared to normal samples. Twelve miRNAs, which had been selected based on statistically different expression level, were finally validated. In PMF granulocytes, levels of miR-31, -150, and -95 were significantly lower, while those of miR-190 significantly greater, than control and PV or ET samples; on the other hand, miR-34a, -342, -326, -105, -149, and -147 were similarly reduced in patients with PMF, PV, or ET compared to controls. Increased expression of miR-182 and -183 correlated with JAK2(617V>F) allele burden. Three in silico-predicted putative target genes (DTR, HMGA2, and MYB), showed deregulated expression in PMF granulocytes that correlated with expression level of regulatory miRNA.Conclusions. A defined miRNA profile distinguishes PMF granulocytes from those of normal subjects and, partially, also from PV or ET patients. (C) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.