miR-424 和 miR-155 在细胞遗传学正常的急性髓系白血病中的失调表达：与 NPM1 和 FLT3 突变状态的相关性。
MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status.
机构信息
Laboratory of Neuro-Oncohematology, Santa Lucia Foundation, Rome, Italy.
出版信息
J Hematol Oncol. 2012 Jun 8;5:26. doi: 10.1186/1756-8722-5-26.
BACKGROUND
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.
FINDINGS
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.
CONCLUSIONS
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.
背景
MicroRNA 在正常造血过程中起着核心作用，并且在急性髓系白血病（AML）中失调。本研究的目的是通过 qRT-PCR 检测在 48 例核型正常的 AML 患者中涉及髓样分化的 miRNAs（miR-424、miR-155、miR-223、miR-17-5p）的表达情况，这些患者的 NPM1 和/或 FLT3 突变情况得到了很好的描述。为了验证数据，我们使用了三种归一化方法。
结果
我们发现，无论 FLT3 状态如何，NPM1mutA 的 AML 中 miR-424 下调。相反，在有或没有 NPM1 突变的 FLT3 内部串联重复（ITD）患者中，miR-155 上调。在分析 miR-223 和 miR-17-5p 与 FLT3 和 NPM1 状态的关系时，没有发现显著的相关性。
结论
本研究支持这样一种观点，即 CN-AML 的主要遗传亚群与不同的 miRNA 特征相关，并表明 miR-424 和 miR-155 的失调分别涉及 NPM1 和 FLT3-ITD 突变的 CN-AML 的发病机制。
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