MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia
MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia
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DOI：
10.1073/pnas.0709313104
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发表时间：
2007-12-11
影响因子：
11.1
通讯作者：
Chen, Jianjun
中科院分区：
文献类型：
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作者：
Mi, Shuangli;Lu, Jun;Chen, Jianjun
急性淋巴细胞白血病（ALL）是最常见的儿童癌症，而急性髓细胞白血病（AML）是成人最常见的急性白血病。一般来说，ALL 的预后比 AML 更好。为了了解 ALL 和 AML 之间白血病发生的不同机制并确定诊断和治疗的标记物，我们进行了大规模全基因组 microRNA (miRNA、miR) 表达谱分析，并鉴定了 ALL 和 AML 之间差异表达的 27 个 miRNA。其中，与AML相比，在ALL中miR-128a和-128b显着过表达，而let-7b和miR-223显着下调。它们是 ALL 和 AML 之间最具区别性的 miRNA。使用这些 miRNA 中至少两个的表达特征，诊断 ALL 和 AML 的准确率达到 >95%。通过对涵盖大多数常见细胞遗传学亚型的 98 个急性白血病样本以及 10 个正常对照样本进行大规模实时 PCR，进一步验证了这四种 miRNA 的差异表达模式。此外，我们发现 ALL 中 miR-128 的过度表达至少部分与启动子低甲基化有关，而不与其基因组位点的扩增有关。综上所述，我们发现，只要两个 miRNA 的表达特征就可以准确区分 ALL 和 AML，并且表观遗传调控可能在急性白血病中 miRNA 表达的调控中发挥重要作用。
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, whereas acute myeloid leukemia (AML) is the most common acute leukemia in adults. In general, ALL has a better prognosis than AML. To understand the distinct mechanisms in leukemogenesis between ALL and AML and to identify markers for diagnosis and treatment, we performed a large-scale genomewide microRNA (miRNA, miR) expression profiling assay and identified 27 miRNAs that are differentially expressed between ALL and AML. Among them, miR-128a and -128b are significantly overexpressed, whereas let-7b and miR-223 are significantly down-regulated in ALL compared with AML. They are the most discriminatory miRNAs between ALL and AML. Using the expression signatures of a minimum of two of these miRNAs resulted in an accuracy rate of >95% in the diagnosis of ALL and AML. The differential expression patterns of these four miRNAs were validated further through large-scale real-time PCR on 98 acute leukemia samples covering most of the common cytogenetic subtypes, along with 10 normal control samples. Furthermore, we found that overexpression of miR-128 in ALL was at least partly associated with promoter hypomethylation and not with an amplification of its genomic locus. Taken together, we showed that expression signatures of as few as two miRNAs could accurately discriminate ALL from AML, and that epigenetic regulation might play an important role in the regulation of expression of miRNAs in acute leukemias.