miR-34a/b/c表达与老年急性髓系白血病患者治疗反应及生存预后的关联分析

目的:评估骨髓单个核细胞中miR-34a/b/c表达水平与老年急性髓系白血病(acute myeloid leukemia,AML)患者临床特征及生存预后的关联。方法:连续纳入91例接受化疗的老年AML初治患者,同时纳入21例非血液恶性疾病患者作为对照者。采用荧光定量PCR(Quantitative real time polymerase chain reaction,qPCR)检测患者和对照者骨髓单个核细胞miR-34a/b/c的相对表达量。所有老年AML患者均根据自身疾病状况以及危险分级,选择接受常规诱导治疗方案,而后评估患者治疗反应。记录患者无事件生存期(event-free survival,EFS)及总体生存期(overall survival,OS)。结果:老年AML患者组的miR-34a和miR-34b水平显著低于对照组(P值均<0.01),而miR-34c水平在两组间无差异(P>0.05)。miR-34a高表达与无FLT3-ITD突变(P<0.05)和较低的危险分级(P<0.05)相关,miR-34b高表达与正常核型(P<0.05)、伴CEBPA双突变(P<0.01)、伴NPM1突变(P<0.05)和WBC计数≤10×109/L(P<0.05)相关,而miR-34c表达水平与患者病理特征均无关联(均P>0.05)。此外,miR-34a高表达与老年AML患者高的CR率(P<0.05)、长的EFS(P<0.01)及好的OS(P<0.01)相关,而miR-34b/c表达水平与患者的CR率、EFS及OS期均无关联(均P>0.05)。结论:miR-34a/b在老年AML患者中低表达,且它们高表达与患者良好的表现临床相关,其中miR-34a高表达还可以在一定程度上预测老年AML患者生存预后。

Correlation of MiR-34a/b/c Expression with Treatment Response and Prognosis of Elderly Patients with Acute Myeloid Leukemia

Objective:To investigate the relate of miR-34 a/b/c expression with clinical features and prognosis in elderly patients with acute myeloid leukemia(AML).Methods:91 elderly patients with AML who consecutively underwent chemotherapy were enrolled in AML group,and 21 patients with non-hematologic malignancies were consider as controls.MiR-34 a/b/c expression in bone marrow mononuclear cells(BMMNC)were detected by quantitative polymerase chain reaction(qPCR).All elderly AML patients received the routine induction chemotherapy based on their disease state and risk stratification.The treatment response was assessed.Overall survival(OS)time and eventfree survival(EFS)time were recorded.Results:The median miR-34 a and miR-34 b(all P<0.01)levels in the elderly AML group were lower than those in the control group,while miR-34 c level was not different between two groups(P>0.05).MiR-34 a high expression correlated with non FLT3-ITD mutation(P<0.05)and lower-risk stage(P<0.05)in elderly AML patients,miR-34 b high expression correlated with normal karyotype(NK)(P<0.05),CEBPA double mutation(P<0.01),NPM1 mutation(P<0.05),and WBC count≤10×109/L(P<0.05),while miR-34 c expression did not correlate with clinical features of patients(all P>0.05).In addition,the miR-34 a high expression correlated with a high CR rate(P<0.05),long EFS(P<0.01)time and OS time(P<0.01)in elderly AML patients,while miR-34 b/c expressions not correlated with CR rate,EFS and OS time in patients(all P>0.05).Conclusion:The miR-34 a/b are low expressed in elderly AML patients,which associates with good clinical manifisfation of patients,and the miR-34 a high expression can predict a good prognosis of elderly AML patients to some extent.