Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia
Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia
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DOI：
10.3324/haematol.2009.020636
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发表时间：
2010-08-01
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影响因子：
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通讯作者：
Rasko, John E. J.
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文献类型：
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作者：
Flamant, Stephane;Ritchie, William;Rasko, John E. J.
研究背景微RNA（micro-RNAs，miRNAs）通过破坏靶基因转录本的稳定性并抑制其翻译来调控基因表达。在包括慢性髓性白血病在内的许多人类癌症中已经描述了miRNA的异常表达。目前新诊断的慢性髓细胞白血病的一线治疗是甲磺酸伊马替尼，它通常产生快速的血液学反应。然而，伊马替尼对体内miRNA表达的影响还没有得到彻底的examined.Design和MethodsUsing的TaqMan低密度阵列系统，我们分析了miRNA的表达在血液样本中的新诊断的慢性粒细胞白血病患者之前和伊马替尼治疗的前两周内。使用定量实时PCR来验证连续的原发性慢性髓性白血病样本中伊马替尼调节的miRNA（n=11，加上12个额外的验证患者）。根据miRNA表达的变化进行生物信息学靶基因预测分析。结果伊马替尼治疗两周后，miR-150和miR-146 a的表达增加，miR-142- 3 p和miR-199 b-5 p的表达减少（中位数变化3倍）。显著相关（P
BackgroundMicro-RNAs (miRNAs) control gene expression by destabilizing targeted transcripts and inhibiting their translation. Aberrant expression of miRNAs has been described in many human cancers, including chronic myeloid leukemia. Current first-line therapy for newly diagnosed chronic myeloid leukemia is imatinib mesylate, which typically produces a rapid hematologic response. However the effect of imatinib on miRNA expression in vivo has not been thoroughly examined.Design and MethodsUsing a TaqMan Low-Density Array system, we analyzed miRNA expression in blood samples from newly diagnosed chronic myeloid leukemia patients before and within the first two weeks of imatinib therapy. Quantitative real-time PCR was used to validate imatinib-modulated miRNAs in sequential primary chronic myeloid leukemia samples (n=11, plus 12 additional validation patients). Bioinformatic target gene prediction analysis was performed based on changes in miRNA expression.ResultsWe observed increased expression of miR-150 and miR-146a, and reduced expression of miR-142-3p and miR-199b-5p (3-fold median change) after two weeks of imatinib therapy. A significant correlation (P