miR-181a表达在慢性粒细胞白血病早期疗效预测中的临床意义

Clinical significance of miR-181a expression in early prognosis of chronic myelogenous leukemia

目的探讨治疗前外周血单个核细胞miR-181a表达与慢性粒细胞白血病慢性期(CML-CP)患者接受伊马替尼治疗3个月、6个月反应性的预测价值。方法选择2017年1月至2017年12月间在德阳市人民医院血液科确诊并接受伊马替尼治疗的95例CML-CP患者,收集治疗前、治疗3个月、6个月后外周血单个核细胞并提取总RNA,采用实时荧光定量PCR(QPCR)检测miR-181a的表达水平。比较治疗前后miR-181a表达的变化,并分析与伊马替尼治疗3个月、6个月后获得临床反应的关系。采用单因素和多因素Logistic回归模型分析影响患者获得6个月完全细胞遗传学反应(CCyR)的因素。结果治疗前CML-CP患者外周血单个核细胞miR-181a表达水平为0.73±0.26,中位表达水平为0.72,治疗3个月、6个月后miR-181a表达水平较治疗前逐渐升高(P<0.05)。48例患者miR-181a表达量≤0.72,为低表达组,其余47例为高表达组。低表达组患者治疗6个月后CCyR获得率为77.08%(37/48),高于高表达组(P<0.05)。单因素和多因素Logistic回归模型结果显示,治疗前和治疗3个月单个核细胞miR-181a表达水平是CML-CP患者治疗6个月获得CCyR的独立影响因素(P<0.05)。结论伊马替尼治疗可上调CML-CP患者外周血单个核细胞miR-181a表达水平,并且治疗前miR-181a低表达者伊马替尼早期反应性更好,可能是影响早期伊马替尼治疗反应的独立因素。

Objective To detect the changes of miR-181a in mononuclear cells in chronic phase of chronic myeloid leukemia(CML-CP)patients with imatinib treatment for 3,6 months,and analyze the prediction of baseline miR-181a value on the response to imatinib.Methods A total of 95 CML-CP patients treated with imatinib more than 6 months were recruited.Peripheral mononuclear cells were collected and monitored at 3 and 6 months after imatinib treatment.The expression of miR-181a in mononuclear cells levels were measured by QPCR.The influence factors of complete cytogenetic response(CCyR)at 6 months were analyzed by univariate and multivariate Logistic regression.Results The expression of miR-181a in mononuclear cells before imatinib was(0.73±0.26),lower than that at 3 and 6 months after imatinib treatment.There were 48 patients with miR-181a levels≤0.72(the median value of miR-181a)as low group and 47 patients with miR-181a>0.72 as high group.Thirty-seven patients(77.08%)in low group achieved CCyR at 6 months,higher than that in high group(P<0.05),while no difference of complete hematologic response(CHR)at 3 months and major molecular response(MMR)at 6 months were seen between low group and high group(P>0.05).The univariate and multivariate Logistic regression showed that miR-181a before treatment or after 3 months of treatment was the independent factor of CCyR at 6 months in CML-CP patients treated with imatinib(P<0.05).Conclusion There are significant evidences that CML-CP patients with low miR-181a could achieve the better response to imatinib in early stage,which might be used as a predictor of imatinib treatment.