MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia
MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia
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DOI：
10.1182/blood-2008-01-133355
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发表时间：
2008-05-15
期刊：
影响因子：
20.3
通讯作者：
Lowenberg, Bob
中科院分区：
文献类型：
--
作者：
Jongen-Lavrencic, Mojca;Sun, Su Ming;Lowenberg, Bob
急性髓系白血病（AML）是一种高度多样化的疾病，其特征是各种细胞遗传学和分子异常。 MicroRNA 是小的非编码 RNA，在骨髓分化过程中表现出可变表达。使用定量逆转录聚合酶链反应 (RT-PCR) 对 260 种人类 microRNA 进行评估，评估了 215 例新诊断和（细胞）遗传学定义的 AML 患者骨髓母细胞中的 MicroRNA 表达。在同一系列中，建立了 mRNA 基因表达谱，从而可以直接比较 microRNA 和 mRNA 表达。我们表明，无监督分析后的 microRNA 表达谱揭示了与 AML 的细胞遗传学和分子亚型（即具有 t(8;21)、t(15;17)、inv(16)、NPM1 和 CEBPA 突变的 AML）相关的独特 microRNA 特征。鉴定出 AML 遗传亚型的显着差异表达的 microRNA。具有已知致癌和肿瘤抑制功能的特定 microRNA，例如 microRNA-155、microRNA-21 和 let-7，似乎与特定亚型相关。选定的 microRNA 组的组合可以预测细胞遗传学正常的 AML，其中 NPM1、CEBPA 和 FLT3-ITD 基因发生突变，其准确度与基因表达谱定义的 mRNA 探针组组合相似。 MicroRNA 表达显然与 AML 的异质病理学具有特定关系。独特的 microRNA 特征似乎在 AML 的临床诊断中具有潜在价值。
Acute myeloid leukemia (AML) is a highly diverse disease characterized by various cytogenetic and molecular abnormalities. MicroRNAs are small noncoding RNAs that show variable expression during myeloid differentiation. MicroRNA expression in marrow blasts in 215 cases of newly diagnosed and (cyto)genetically defined AML was assessed using quantitative reverse-transcription-polymerase chain reaction (RT-PCR) for 260 human microRNAs. In the same series, mRNA gene expression profiles were established, allowing a direct comparison between microRNA and mRNA expression. We show that microRNA expression profiling following unsupervised analysis reveals distinctive microRNA signatures that correlate with cytogenetic and molecular subtypes of AML (ie, AMLs with t(8;21), t(15;17), inv(16), NPM1, and CEBPA mutations). Significantly differentially expressed microRNAs for genetic subtypes of AML were identified. Specific microRNAs with established oncogenic and tumor suppressor functions, such as microRNA-155, microRNA-21, and let-7, appear to be associated with particular subtypes. Combinations of selected sets of microRNAs could predict cytogenetically normal AML with mutations in the genes of NPM1 and CEBPA and FLT3-ITD with similar accuracy as mRNA probe set combinations defined by gene expression profiling. MicroRNA expression apparently bears specific relationships to the heterogeneous pathobiology of AML. Distinctive microRNA signatures appear of potential value in the clinical diagnosis of AML.