COX-2在AML中的表達意義及與野生型P53相關(guān)性的研究
發(fā)布時間：2019-06-09 13:52
【摘要】：目的通過檢測初發(fā)和復(fù)發(fā)急性髓系白血病(Acute myeloid leukemia,AML)患者中環(huán)氧化酶-2(Cyclooxygenase-2,COX-2)基因和抑癌基因野生型p53(Wild type p53,WT p53)的表達水平,分析二者的表達特點和相關(guān)性;并研究其與患者臨床特征、不同危險度和不同亞型的相關(guān)性,旨在探討可能導(dǎo)致AML復(fù)發(fā)的機制。方法(1)收集2016年3月至9月來自山西醫(yī)科大學(xué)第二醫(yī)院血液科的WT p53無突變的骨髓標(biāo)本共82例。AML患者61例,除外急性早幼粒細(xì)胞白血病(Acute promyelocytic leukemia,APL),包括初發(fā)組37例和復(fù)發(fā)組24例;以及21例正常對照(包括缺鐵性貧血14例,原發(fā)性免疫性血小板減少癥7例);(2)采用實時熒光定量聚合酶鏈反應(yīng)(Quantitative real-time PCR,RT-q PCR)方法和Western blot方法,檢測骨髓標(biāo)本中COX-2和WT p53在m RNA和蛋白質(zhì)水平的表達情況;(3)采用SPSS 22.0和Graph Pad Prism 5.0軟件進行統(tǒng)計分析和繪圖。結(jié)果(1)經(jīng)RT-q PCR和Western blot分析,表明COX-2在AML患者中呈過表達,且在復(fù)發(fā)組中明顯高于初發(fā)組(P0.05);而WT p53表達隨疾病進展而降低(P0.05);(2)在初發(fā)組和復(fù)發(fā)組中COX-2和WT p53表達均呈負(fù)相關(guān)(P0.05),正常組中無差異(P0.05);(3)不同的FAB亞型患者中均有COX-2表達增高和WT p53表達下降的趨勢,但僅M5型的患者有統(tǒng)計學(xué)意義(P0.05);(4)與中低危組患者相比,高危組的患者在不同疾病狀態(tài)下COX-2表達均明顯增高(P0.05);(5)在初發(fā)組和復(fù)發(fā)組中,COX-2、WT p53的表達與年齡、性別、血小板計數(shù)、血紅蛋白濃度均無關(guān)。在復(fù)發(fā)組中,隨著外周血白細(xì)胞計數(shù)和骨髓原始細(xì)胞比例增高以及異常染色體,COX-2表達增高,而WT p53表達下降(P0.05)。結(jié)論COX-2作為慢性非可控性炎癥介質(zhì),在AML中呈過表達,負(fù)反饋調(diào)控WT p53導(dǎo)致AML的發(fā)生發(fā)展;兩者表達與高危組、外周血白血病計數(shù)、骨髓原始細(xì)胞比例和異常染色體有關(guān)。
[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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R733.71
本文編號：2495601
[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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R733.71
【參考文獻】
相關(guān)期刊論文 前7條
1 劉文斌;曹廣文;;癌癥進化發(fā)育學(xué):基于炎-癌轉(zhuǎn)化研究的新學(xué)說[J];中國腫瘤生物治療雜志;2017年02期
2 王曉軍;茹甫毅;吳雙有;朱衛(wèi)民;田培軍;;COX-2、bFGF及TGFβ1在慢性粒細(xì)胞白血病中的表達及其意義[J];現(xiàn)代腫瘤醫(yī)學(xué);2017年04期
3 化范例;王玲燕;趙鑫;李瑩;鄔揚炯;高松;;選擇性COX-2抑制劑塞來昔布抑制B細(xì)胞淋巴瘤細(xì)胞株MDR-1及Bcl-2的mRNA表達并增強表柔比星的抗腫瘤作用[J];中國癌癥雜志;2015年06期
4 Naoki Hashimoto;;Effects of bile acids on cyclooxygenase-2 expression in a rat model of duodenoesophageal anastomosis[J];World Journal of Gastroenterology;2014年21期
5 Jian Cheng;Xiao-Ming Fan;;Role of cyclooxygenase-2 in gastric cancer development and progression[J];World Journal of Gastroenterology;2013年42期
6 戴海霞;張曉燕;徐開俊;陳建華;;非甾體抗炎藥研究的最新進展[J];藥物生物技術(shù);2012年01期
7 隋華;周利紅;劉宣;殷佩浩;周寧;王炎;孫玨;范忠澤;李琦;;COX-2介導(dǎo)MDR1/P-gp調(diào)控人結(jié)腸癌細(xì)胞多藥耐藥的研究[J];中國癌癥雜志;2011年04期
，本文編號：2495601
本文鏈接：http://sikaile.net/yixuelunwen/zlx/2495601.html
最近更新
教材專著
