COX-2在AML中的表达意义及与野生型P53相关性的研究

发布时间：2019-06-09 13:52

【摘要】：目的通过检测初发和复发急性髓系白血病(Acute myeloid leukemia,AML)患者中环氧化酶-2(Cyclooxygenase-2,COX-2)基因和抑癌基因野生型p53(Wild type p53,WT p53)的表达水平,分析二者的表达特点和相关性;并研究其与患者临床特征、不同危险度和不同亚型的相关性,旨在探讨可能导致AML复发的机制。方法(1)收集2016年3月至9月来自山西医科大学第二医院血液科的WT p53无突变的骨髓标本共82例。AML患者61例,除外急性早幼粒细胞白血病(Acute promyelocytic leukemia,APL),包括初发组37例和复发组24例;以及21例正常对照(包括缺铁性贫血14例,原发性免疫性血小板减少症7例);(2)采用实时荧光定量聚合酶链反应(Quantitative real-time PCR,RT-q PCR)方法和Western blot方法,检测骨髓标本中COX-2和WT p53在m RNA和蛋白质水平的表达情况;(3)采用SPSS 22.0和Graph Pad Prism 5.0软件进行统计分析和绘图。结果(1)经RT-q PCR和Western blot分析,表明COX-2在AML患者中呈过表达,且在复发组中明显高于初发组(P0.05);而WT p53表达随疾病进展而降低(P0.05);(2)在初发组和复发组中COX-2和WT p53表达均呈负相关(P0.05),正常组中无差异(P0.05);(3)不同的FAB亚型患者中均有COX-2表达增高和WT p53表达下降的趋势,但仅M5型的患者有统计学意义(P0.05);(4)与中低危组患者相比,高危组的患者在不同疾病状态下COX-2表达均明显增高(P0.05);(5)在初发组和复发组中,COX-2、WT p53的表达与年龄、性别、血小板计数、血红蛋白浓度均无关。在复发组中,随着外周血白细胞计数和骨髓原始细胞比例增高以及异常染色体,COX-2表达增高,而WT p53表达下降(P0.05)。结论COX-2作为慢性非可控性炎症介质,在AML中呈过表达,负反馈调控WT p53导致AML的发生发展;两者表达与高危组、外周血白血病计数、骨髓原始细胞比例和异常染色体有关。
[Abstract]:Objective to detect the expression of cyclooxygenase-2 (Cyclooxygenase-2,COX-2) gene and tumor suppressor gene wild type p53 (Wild type p53, WT p53) in patients with primary and recurrent acute myeloid leukemia (Acute myeloid leukemia,AML). The expression characteristics and correlation of the two were analyzed. In order to explore the mechanism of recurrence of AML, the correlation between it and clinical characteristics, different risk and different subtypes was studied in order to explore the mechanism of recurrence. Methods (1) A total of 82 bone marrow specimens from the Department of Hematology, second Hospital of Shanxi Medical University from March to September 2016 were collected. 61 patients with acute promyelocytic leukemia (Acute promyelocytic leukemia,APL), 61 patients with acute promyelocytic leukemia, 61 patients with acute promyelocytic leukemia. There were 37 cases in the primary group and 24 cases in the recurrence group. And 21 normal controls (including 14 cases of iron deficiency anemia and 7 cases of primary immune thrombopenia). (2) the expression of COX-2 and WT p53 in bone marrow samples at m RNA and protein levels was detected by real time fluorescence quantitative polymerase chain reaction (Quantitative real-time PCR,RT-q PCR) and Western blot. (3) SPSS 22.0 and Graph Pad Prism 5.0 software were used for statistical analysis and mapping. Results (1) RT-q PCR and Western blot analysis showed that COX-2 was overexpressed in AML patients, and the expression of WT p53 in recurrent group was significantly higher than that in primary group (P 0.05), while the expression of WT p53 decreased with the progress of the disease (P 0.05). (2) there was a negative correlation between the expression of COX-2 and WT p53 in the primary group and the recurrent group (P 0.05), but there was no difference in the normal group (P 0.05). (3) the expression of COX-2 increased and the expression of WT p53 decreased in all patients with different FAB subtypes, but only the patients with M5 type had statistical significance (P 0.05). (4) compared with the middle and low risk group, the expression of COX-2 in the high risk group was significantly higher than that in the middle and low risk group (P 0.05). (5) the expression of COX-2,WT p53 was not related to age, sex, platelet count and hemoglobin concentration in primary and recurrent groups. In the recurrent group, with the increase of peripheral blood leukocyte count and the proportion of bone marrow primordial cells and abnormal chromosomes, the expression of COX-2 increased, while the expression of WT p53 decreased (P 0.05). Conclusion COX-2, as a chronic uncontrollable inflammatory mediator, is overexpressed in AML, and negative feedback regulation of WT p53 leads to the occurrence and development of AML, which is related to high risk group, peripheral blood leukemia count, proportion of bone marrow primordial cells and abnormal chromosomes.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71

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