微RNA-181a在核型正常急性髓系白血病患者中的表达及临床意义

Expression characteristics and prognosis significance of miRNA-181a in acute myeloid leukemia with normal karyotype

目的探讨核型正常急性髓系白血病（CN．AML）患者微RNA（miRNA）-181a的表达水平及其与预后的关系。方法采用实时荧光定量PCR法检测120例初诊原发CN．AML患者骨髓单个核细胞miRNA-181a的表达水平，PCR后采用直接测序方法检测IDH1、IDH2、NPM1、FLT3-ITD、DNMT3A和CEBPa突变。分析miRNA-181a表达与基因突变、其他临床指标和预后的关系。结果miRNA-181a高表达组和低表达组患者中位总生存（OS）时间分别为25．0和15．0个月（P〈0．05）；中位无复发生存（RFS）时间分别为21．4和11．2个月（P〈0．001）。miRNA-181a高表达组患者HGB水平、完全缓解率、NPM1野生型比例均较低表达组高，差异有统计学意义（P值均〈0．05）；用Cox回归模型多因素分析显示，miRNA-181a高表达是影响CN-AML患者预后的独立因素（HR=2．219，95％C11．601～2．432，P=0．018）。结论miRNA-181a高表达是独立于临床指标和高频基因突变的预后良好的标志物，miRNA-181a表达水平可作为CN—AML预后的重要指标。

Objective To study the expression of miRNA-181a in acute myeloid leukemia （AML） patients with normal karyotype to probe its prognosis significance. Methods The expression level of miRNA- 181a in bone marrow mononuelear cells of 120 de novo AML patients with normal karyotype was detected by real time fluorescence quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2, NPM1, FLT3-ITD, DNMT3A and CEBPct mutations in CN-AML patients after PCR. The relationship between miRNA-181a expression and gene mutation, the clinical parameters and prognosis were analyzed. Results The rates of overall survival （OS） in high expression and low expression groups were 25.0 months and 15.0 months, respectively（P 〈 0.05）. Relapse free survival （RFS） in high expression and low expression groups were 21.4 months and 11.2 months, respectively （P 〈 0.05 ）. Significantly higher level hemoglobin, complete remission rate and proportion of wild type NPM1 expression in the high expression of miRNA-181a group were observed when compared with the lower expression of miRNA- 181 a group （P 〈 0.05 ）. Multivariate Cox regression analysis showed miRNA- 181 a overexpression was an independent prognostic factor for CN- AML （HR = 2.219, 95% CI 1.601 ~ 2.432, P = 0.018）. Conclusion Higher expression of miRNA-181 a was a good prognostic factor independent of clinical parameters and high frequency gene mutations, which implicated that the miRNA-181 a expression level could be used as an important prognostic indicator of AML patients with normal karyotype.