MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status.

MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status.
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DOI:
10.1186/1756-8722-5-26
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发表时间:
2012-06-08
影响因子:
28.5
通讯作者:
Lo-Coco F
Lo-Coco F
中科院分区:
医学1区
文献类型:
--
作者:
Faraoni I;Laterza S;Ardiri D;Ciardi C;Fazi F;Lo-Coco F

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MicroRNA在正常造血中起中心作用,在急性髓性白血病(AML)中不受调节。该研究的目的是通过qRT-PCR研究48例细胞遗传学正常的AML患者中参与髓系分化的mirna (miR-424, miR-155, miR-223, miR-17-5p)的表达,这些患者具有NPM1和/或FLT3突变的特征。三种类型的归一化用于数据验证。我们发现miR-424在具有NPM1mutA的aml中下调,无论FLT3状态如何。相反,miR-155在具有或不具有NPM1突变的FLT3内部串联重复(ITD)患者中表现出上调。通过分析miR-223和miR-17-5p与FLT3和NPM1状态的关系,未发现显著相关性。该研究支持了CN-AML的主要遗传亚群与不同的miRNA特征相关的观点,并表明miR-424和miR-155的失调分别参与了NPM1和FLT3-ITD突变的CN-AML的发病机制。
MicroRNA have a central role in normal haematopoiesis and are deregulated in acute myeloid leukaemia (AML). The purpose of the study was to investigate by qRT-PCR the expression of miRNAs involved in myeloid differentiation (miR-424, miR-155, miR-223, miR-17-5p) in 48 patients with cytogenetically normal AML well characterized for NPM1 and/or FLT3 mutations. Three types of normalization were used for the data validation. We found that miR-424 was down-modulated in AMLs with NPM1mutA regardless of FLT3 status. On the contrary, miR-155 showed up-regulation in patients with FLT3 internal tandem duplications (ITD) with or without NPM1 mutations. No significant associations were found by analyzing miR-223 and miR-17-5p in relation to FLT3 and NPM1 status. This study supports the view that major genetic subsets of CN-AML are associated with distinct miRNA signatures and suggests that miR-424 and miR-155 deregulation is involved in the pathogenesis of CN-AML with NPM1 and FLT3-ITD mutations, respectively.
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