Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China.
Clin Biochem. 2013 Jan;46(1-2):49-53. doi: 10.1016/j.clinbiochem.2012.09.002. Epub 2012 Sep 12.
As a member of miR-29 family, miR-29a can act as either oncogene or tumor suppressor. However, its expression patterns in acute myeloid leukemia (AML) are controversial according to previous studies. Thus, the aim of this study was to determine the expression and clinical significance of miR-29a in pediatric AML.
Expression levels of miR-29a in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. The prognostic values of miR-29a in pediatric AML were also analyzed.
Compared with normal controls, we demonstrated a significantly decreased expression of miR-29a in the bone marrow of pediatric AML patients (P<0.001). The expression levels of miR-29a were significantly lower in French-American-British classification subtype M7 than in other subtypes (P<0.001) and differed significantly across cytogenetic risk groups (P=0.002) with high miR-29a expression among those with favorable karyotypes. Moreover, low miR-29a expression was significantly associated with shorter relapse-free (P<0.001) and overall (P=0.008) survival in pediatric AML patients. Cox proportional hazards multivariate analysis of the univariate predictors identified cytogenetic risk and miR-29a expression as independent prognostic factors for relapse-free survival and overall survival. More interestingly, the prognostic value of miR-29a expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics.
Our data indicate for the first time that the down-regulation of miR-29a was associated with advanced clinical features and poor prognosis of pediatric AML patients, suggesting that miR-29a down-regulation may be used as an unfavorable prognostic marker in pediatric AML.
作为 miR-29 家族的一员，miR-29a 可以作为癌基因或肿瘤抑制因子发挥作用。然而，根据之前的研究，其在急性髓系白血病（AML）中的表达模式存在争议。因此，本研究旨在确定 miR-29a 在儿科 AML 中的表达及其临床意义。
通过实时定量 PCR 检测 106 例新诊断的儿科 AML 患者骨髓单个核细胞中 miR-29a 的表达水平。并分析 miR-29a 在儿科 AML 中的预后价值。
与正常对照组相比，我们发现儿科 AML 患者骨髓中 miR-29a 的表达显著降低（P<0.001）。miR-29a 的表达水平在 French-American-British 分类亚型 M7 中明显低于其他亚型（P<0.001），且在细胞遗传学风险组之间存在显著差异（P=0.002），具有良好核型的患者中 miR-29a 表达较高。此外，低 miR-29a 表达与儿科 AML 患者无复发生存（P<0.001）和总生存（P=0.008）显著相关。对单因素预测因素的 Cox 比例风险多因素分析确定细胞遗传学风险和 miR-29a 表达是无复发生存和总生存的独立预后因素。更有趣的是，miR-29a 表达的预后价值在细胞遗传学中危亚组中更为明显。
我们的数据首次表明，miR-29a 的下调与儿科 AML 患者的晚期临床特征和不良预后相关，表明 miR-29a 下调可能作为儿科 AML 的不利预后标志物。
