初治急性髓系白血病患者中MDR1和Nrf2基因的表达研究

Expression of MDR1 and Nrf2 genes on initial treatment patients with acute myeloid leukemia

目的探讨急性髓系白血病（AML）患者MDR1和Nrf2基因表达水平及其临床意义。方法选择2011年10月至2014年1月南方医科大学南方医院血液科110例初治AML患者,其中男性66例,女性44例;年龄14~77岁,中位年龄36岁。通过实时荧光定量聚合酶链反应（PCR）方法联合检测患者MDR1和Nrf2基因的表达水平,分析其表达水平与疾病特征及临床疗效之间的关系。结果以110例初治AML患者MDR1和Nrf2基因表达量的中位数为分界点,将患者分别分为MDR1基因低表达组和MDR1基因高表达组及Nrf2基因低表达组和Nrf2基因高表达组各55例,而初治AML患者MDR1和Nrf2基因表达水平在不同分层的年龄、性别、法国（France）、美国（American）和英国（Britain）（FAB）分型、外周血象、骨髓原始细胞比例、遗传学危险度分层、免疫分型CD34表达间差异无统计学意义（P〉0.05）。MDR1基因低表达组完全缓解（CR）率和总生存（OS）率均显著高于MDR1基因高表达组（P=0.032、0.045）,而Nrf2基因低表达组和Nrf2基因高表达组CR率和OS率差异无统计学意义（P〉0.05）。在MDR1基因低表达组患者中Nrf2基因表达水平高、低两组患者CR率及OS率差异均无统计学意义（P〉0.05）。但在MDR1基因高表达组患者中Nrf2基因高表达组患者CR率和OS率皆优于Nrf2基因低表达组患者（P=0.007和P=0.001）。结论 MDR1基因是AML预后差的指标之一,Nrf2基因不同表达水平患者的危险度分层、疗效、预后差异均无统计学意义;但在MDR1基因高表达组患者中Nrf2基因高表达可能是预后好的指标。

Objective To investigate the expression and clinical significance of MDR1 gene and Nrf2 gene in patients with acute myeloid leukemia（AML）. Methods From October 2011 to January 2014, a total of 110 initial treatment AML patients were enrolled, included 66 males and 44 females, aged 14 - 77 years old with median age of 36 years old. The real-time reverse transcription- polymerase chain reaction（RT-PCR） was used to detect the expression levels of MDR1 gene and Nrf2 gene, and the relationship between expression level of disease characteristics and clinical efficacy was analyzed. Results Median expression of MDR1 gene and Nrf2 gene were taken as demarcation point, 110 initial treatment AML patients were divided into MDR1 gene low expression, MDR1 gene high expression group and Nrf2 gene low expression, Nrf2 gene high expression group, n = 55. No significant differences of MDR1 gene and Nrf2 gene were found in age, gender, in classification of France, American and Britain（FAB）, peripheral blood, blast counts of bone marrow, genetics, risk stratification, immunotype and CD34 proportion（P 〉 0.05）. The complete remission（CR） and overall survival（OS） rates in MDR1 gene low expression group were significantly higher than that of MDR1 gene high expression group（P = 0.032, 0.045）. There were no significant differences between CR and OS of Nrf2 gene low expression group and that of Nrf2 gene high expression group（P 〉 0.05）. In MDR1 low expression group, there were no significant differences between the CR and OS rates of both Nrf2 gene expression groups, while in MDR1 high expression group, CR and OS rates in Nrf2 gene high expression group were better than that in Nrf2 gene low expression group （P = 0.007 and P = 0.001）. Conclusion It is demonstrated that MDR1 gene is one of poor prognostic indicator of AML. There are no statistical significant differences between Nrf2 gene expression groups in risk stratification, curative effect and prognosis, while Nrf2 gene high expression in high-MDR1 gene patients could be good prognostic index.