MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia
MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia
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DOI：
10.1182/blood-2007-07-098749
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发表时间：
2008-03-15
期刊：
影响因子：
20.3
通讯作者：
Croce, Carlo M.
中科院分区：
文献类型：
--
作者：
Garzon, Ramiro;Volinia, Stefano;Croce, Carlo M.
MicroRNA（miRNAs）是一种19 - 25个核苷酸的小RNA，是基因表达的负调节因子。为了确定miRNA是否与急性髓系白血病（AML）的细胞遗传学异常和临床特征相关，我们使用微阵列平台评估了CD 34（+）细胞和122例未经治疗的成人AML病例的miRNA表达。在使用一组管家基因进行背景扣除和标准化后，使用微阵列的显著性分析来分析数据。一组独立的60名未经治疗的AML患者被用来验证使用实时聚合酶链反应的结果签名。我们鉴定了几种在CD 34+正常细胞和AML样品之间差异表达的miRNA。miRNA表达也与选定的细胞遗传学和分子异常密切相关，如t（11 q23），孤立的8号三体和FLT 3-ITD突变。此外，miR-191和miR-199 a高表达的患者的总体和无事件生存率显著低于低表达的AML患者（总体生存率：miR-191，P = 0.03; miR-199 a，P = 0.001，考克斯回归）。总之，AML中的miRNA表达与细胞遗传学和FLT 3-ITD突变密切相关。一小部分miRNA与生存相关。
MicroRNAs (miRNAs) are small RNAS of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34(+) cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34+ normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-ITD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-ITD mutations. A small subset of miRNAs is correlated with survival.