Prognostic Significance of Expression of a Single MicroRNA, miR-181a, in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
Prognostic Significance of Expression of a Single MicroRNA, miR-181a, in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
复制标题
DOI：
10.1200/jco.2010.29.2953
复制
发表时间：
2010-12-20
影响因子：
45.3
通讯作者：
Bloomfield, Clara D.
中科院分区：
文献类型：
--
作者：
Schwind, Sebastian;Maharry, Kati;Bloomfield, Clara D.
目的评价单个microRNA（miR-181 a）表达水平在细胞遗传学正常的急性髓系白血病（CN-AML）中的预后意义。并深入了解miR-181 a的致白血病作用。使用俄亥俄州州立大学综合癌症中心3.0版阵列在187名年轻患者中测量治疗前骨髓中181 a的表达。（< 60岁）CN-AML成人。集中评估是否存在其他分子粘附因子。与miR-181 a表达相关的基因表达谱使用微阵列获得，并通过Gene-Ontology analysis.ResultsHigher miR-181 a表达与较高的完全缓解（CR）率（P = 0.04），较长的总生存期（OS; P = 0.01）和较长的无病生存期（DFS; P = 0.09）的趋势。miR-181 a的影响在具有FLT 3-内部串联重复（FLT 3-ITD）和/或NPM 1野生型的低分子风险患者中最为显著，其中较高的miR-181 a表达与较高的CR率（P = .009）、较长的DFS（P = .001）和OS（P = .001）相关。在多变量分析中，在整个患者队列和FLT 3-ITD和/或NPM 1野生型患者中，较高的miR-181 a表达与较好的结局显著相关。这些结果也在一组独立的老年（>= 60岁）CN-AML患者中得到验证。一个miR-181 a相关的基因表达谱的特点是丰富的基因通常参与先天immunity.ConclusionTo我们的知识，我们提供了第一个证据表明，一个单一的microRNA，miR-181 a的表达，与CN-AML患者的临床结果，并可能完善其分子风险分类。增加内源性miR-181 a水平的靶向治疗可能代表新的治疗策略。
PurposeTo evaluate the prognostic significance of expression levels of a single microRNA, miR-181a, in the context of established molecular markers in cytogenetically normal acute myeloid leukemia (CN-AML), and to gain insight into the leukemogenic role of miR-181a.Patients and MethodsmiR-181a expression was measured in pretreatment marrow using Ohio State University Comprehensive Cancer Center version 3.0 arrays in 187 younger (< 60 years) adults with CN-AML. Presence of other molecular prognosticators was assessed centrally. A gene-expression profile associated with miR-181a expression was derived using microarrays and evaluated by Gene-Ontology analysis.ResultsHigher miR-181a expression associated with a higher complete remission (CR) rate (P = .04), longer overall survival (OS; P = .01) and a trend for longer disease-free survival (DFS; P = .09). The impact of miR-181a was most striking in poor molecular risk patients with FLT3-internal tandem duplication (FLT3-ITD) and/or NPM1 wild-type, where higher miR-181a expression associated with a higher CR rate (P = .009), and longer DFS (P = .001) and OS (P = .001). In multivariable analyses, higher miR-181a expression was significantly associated with better outcome, both in the whole patient cohort and in patients with FLT3-ITD and/or NPM1 wild-type. These results were also validated in an independent set of older (>= 60 years) patients with CN-AML. A miR-181a-associated gene-expression profile was characterized by enrichment of genes usually involved in innate immunity.ConclusionTo our knowledge, we provide the first evidence that the expression of a single microRNA, miR-181a, is associated with clinical outcome of patients with CN-AML and may refine their molecular risk classification. Targeted treatments that increase endogenous levels of miR-181a might represent novel therapeutic strategies.