miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia
miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia
复制标题
DOI：
10.1182/blood-2012-02-408492
复制
发表时间：
2012-07-12
期刊：
影响因子：
20.3
通讯作者：
Bloomfield, Clara D.
中科院分区：
文献类型：
--
作者：
Eisfeld, Ann-Kathrin;Marcucci, Guido;Bloomfield, Clara D.
高BAALC表达水平与细胞遗传学正常的急性髓性白血病（CN-AML）患者的不良结局相关。最近，在BAALC的内含子1中发现了miR-3151。为了评估miR-3151表达水平的预后意义并深入了解miR-3151与其宿主之间的生物学和预后相互作用，在179名CN-AML患者的预处理血液中测量了miR-3151和BAALC表达。使用微阵列进行基因表达谱分析和miRNA表达谱分析。miR-3151高表达与较短的无病生存期和总生存期相关，而BAALC高表达预测完全缓解失败和较短的总生存期。miR-3151和BAALC均高表达的患者的预后比任一基因或两种基因均低表达的患者差。在基因表达谱分析中，高miR-3151表达者显示参与转录调控、翻译后修饰和癌症途径的基因下调。两个基因FBXL 20和USP 40被验证为直接miR-3151靶标。本研究的结果表明，miR-3151的高表达是CN-AML不良结局的独立预测因子，并且影响与其宿主基因BAALC不同的结局终点。两种标记物的组合鉴定了具有最差结果的患者亚组。内含子miR与其宿主之间的这种相互作用可能具有重要的生物学意义。（血。2012; 120（2）：249-258）
High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications. (Blood. 2012; 120(2):249-258)