【摘要】：目的:本單位血液科課題組前期研究發(fā)現(xiàn)急性髓系白血病(AML)患者與正常人的mi RNA表達(dá)譜存在顯著差異,其中mi R-10a-5p高表達(dá)。本研究通過分析mi R-10a-5p在AML患者骨髓及血清中的表達(dá)情況,探討mi R-10a-5p與AML臨床生物學(xué)特征的關(guān)系及其預(yù)后意義,為mi R-10a-5p在AML的治療及預(yù)后判斷中的作用奠定實(shí)驗(yàn)基礎(chǔ)和提供重要信息。方法:2009年12月至2014年10月收集蘇州大學(xué)附屬第三醫(yī)院(常州市第一人民醫(yī)院)收治的168例AML患者血清標(biāo)本(初治患者108例,完全緩解患者39例,復(fù)發(fā)患者21例)及正常人血清對(duì)照25例;其中男117例,女51例,中位年齡51歲。2013年3月至2014年3月收集65例AML患者骨髓標(biāo)本(初治患者36例,完全緩解患者15例,復(fù)發(fā)患者14例)及正常人骨髓對(duì)照14例;其中男41例,女24例,中位年齡51歲。同時(shí)購(gòu)買急性早幼粒白血病細(xì)胞株HL-60及其阿霉素耐藥細(xì)胞株HL-60/ADR;提取所有標(biāo)本中總RNA,應(yīng)用實(shí)時(shí)定量聚合酶鏈反應(yīng)(RT-PCR)方法檢測(cè)AML患者及對(duì)照組以及細(xì)胞株中mi R-10a-5p的表達(dá)情況;探討其與AML臨床、生物學(xué)特征的關(guān)系及其預(yù)后意義。結(jié)果:HL-60/ADR耐藥株中mi R-10a-5p表達(dá)明顯高于敏感株HL-60(6.8倍,p0.001);初治AML患者血清中mi R-10a-5p表達(dá)高于正常(p0.001),完全緩解組mi R-10a-5p表達(dá)低于初治組(p0.001),復(fù)發(fā)組的表達(dá)量又高于完全緩解組(p0.001),而完全緩解組的表達(dá)與正常組無(wú)明顯統(tǒng)計(jì)學(xué)差異(p0.05);在AML患者骨髓細(xì)胞中mi R-10a-5p表達(dá)與血清標(biāo)本出現(xiàn)同樣的動(dòng)態(tài)變化趨勢(shì);分析ROC(Receiver Operator Characteristic)曲線得出mi R-10a-5p診斷AML的靈敏度為79.6%,特異度為80.0%,ROC曲線下面積為0.831;分析骨髓單個(gè)核細(xì)胞mi R-10a-5p的表達(dá)與血清mi R-10a-5p表達(dá)的關(guān)系,發(fā)現(xiàn)兩組標(biāo)本中mi R-10a-5p的水平呈明顯的正相關(guān);分析血清mi R-10a-5p與臨床指標(biāo)的關(guān)系發(fā)現(xiàn)mi R-10a-5p與年齡(p=0.687)、性別(p=0.837)、白細(xì)胞計(jì)數(shù)(p=0.177)、血紅蛋白濃度(p=0.441)、血小板計(jì)數(shù)(p=0.558)、骨髓原始細(xì)胞數(shù)(p=0.177)、脾腫大(p=0.558)、細(xì)胞遺傳學(xué)(p=0.288)、NPM突變(p=0.319)、CD34陽(yáng)性率(p=0.618)等臨床特征無(wú)明顯相關(guān)性。以mi R-10a-5p的中位數(shù)為界,將所有血清標(biāo)本中初治AML患者分為高表達(dá)組和低表達(dá)組,分析初治患者經(jīng)一療程標(biāo)準(zhǔn)方案誘導(dǎo)化療后,發(fā)現(xiàn)血清mi R-10a-5p高表達(dá)AML患者完全緩解率低于低表達(dá)AML患者(分別為38.8%,59.2%,p=0.043),而且血清mi R-10a-5p高表達(dá)AML患者總體生存率短于低表達(dá)AML患者(p=0.042)。結(jié)論:mi R-10a-5p在AML患者中普遍存在高表達(dá),且在AML疾病發(fā)展過程中呈動(dòng)態(tài)變化,與腫瘤負(fù)荷相關(guān),高表達(dá)的mi R-10a-5p可能是AML預(yù)后不良的生物學(xué)標(biāo)志之一。血清標(biāo)本易于取得,血清mi R-10a-5p水平可以作為觀測(cè)AML疾病發(fā)展的重要指標(biāo)之一。
[Abstract]:Objective: in the previous study of our department of hematology, we found that there was significant difference in mi RNA expression profile between patients with acute myeloid leukemia (AML) and normal subjects, among which mi R-10a-5p was highly expressed. In this study, we analyzed the expression of mi R-10a-5p in bone marrow and serum of AML patients, and explored the relationship between mi R-10a-5p and clinical biological characteristics of AML and its prognostic significance. To lay the experimental foundation and provide important information for the role of mi R-10a-5p in the treatment and prognosis of AML. Methods: from December 2009 to October 2014, serum samples of 168 patients with AML were collected from the third affiliated Hospital of Suzhou University (the first people's Hospital of Changzhou). From March 2013 to March 2014, bone marrow specimens were collected from 65 patients with AML (36 patients with primary treatment and 15 patients with complete remission). There were 14 patients with recurrent bone marrow and 14 normal controls, including 41 males and 24 females with a median age of 51 years. At the same time, the expression of mi R-10a-5p was detected by real-time quantitative polymerase chain reaction (RT-PCR) in patients with acute promyelocytic leukemia (HL-60) and its adriamycin resistant cell line (HL-60/ADR;) by real-time quantitative polymerase chain reaction (RT-PCR). To explore the relationship between AML and clinical and biological characteristics and its prognostic significance. Results the expression of mi R-10a-5p was significantly higher in the% HL-60 / ADR resistant strain than in the sensitive strain HL-60 (6.8-fold p0.001), the expression of mi R-10a-5p in the newly treated AML patients was higher than that in the normal group (p0.001), the expression of mi R-10a-5p in the complete remission group was lower than that in the first treatment group (p0.001), and the expression of mi R-10a-5p in the relapsed group was higher than that in the complete remission group (p0.001). There was no significant difference in the expression of mi R-10a-5p between the complete remission group and the normal group (p0.05). The expression of mi R-10a-5p in the bone marrow cells of AML patients showed the same dynamic trend as the serum samples. The sensitivity and specificity of mi R-10a-5p in the diagnosis of AML were 79.6 and 0.831, respectively. The relationship between the expression of mi R-10a-5p in bone marrow mononuclear cells and the expression of serum mi R-10a-5p was found to be positively related to the level of mi R-10a-5p in the two groups. Analysis of the relationship between serum mi R-10a-5p and clinical indexes showed that the positive rate of CD34 in mi R-10a-5p and age (p0. 687), sex (p0. 837), white blood cell count (p0. 177), hemoglobin concentration (p0. 441), platelet count (p0. 558), bone marrow primordial cell count (p0. 177), splenomegaly (p0. 558), cytogenetics (p0. 288) mutation (p0. 319) and CD34 positive rate (p0. 618) were found. There was no significant correlation in clinical features. According to the median of mi R-10a-5p, the newly treated AML patients were divided into two groups: high expression group and low expression group. It was found that the complete remission rate of patients with high expression of mi R-10a-5p AML was lower than that of patients with low expression of AML (38.8% or 59.2%, respectively), and the overall survival rate of patients with high expression of AML in serum mi R-10a-5p was shorter than that of patients with low expression of AML (p0.042). Conclusion there is a high expression of R-10a-5p in AML patients, and it is a dynamic change during the development of AML. The high expression of mi R-10a-5p may be one of the biological markers of poor prognosis of AML. Serum samples are easy to be obtained, and serum mi R-10a-5p level can be used as an important index to observe the development of AML disease.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R733.71

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