本文關(guān)鍵詞： 急性白血病 WT1基因 標(biāo)志基因 微小殘留病　出處：《大連醫(yī)科大學(xué)》2016年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的:通過(guò)回顧分析初治急性白血病(acute leukemia,AL)患者的臨床資料,研究WT1基因在AL分型中的表達(dá)特點(diǎn);比較WT1基因與其他標(biāo)志基因在病程階段中表達(dá)水平的變化,以判斷兩者間的相關(guān)性;同時(shí)為白血病微小殘留病(minimal r esidual disease,MRD)的監(jiān)測(cè)提供參考意見(jiàn)。方法:采用熒光實(shí)時(shí)定量RT-PCR的方法,對(duì)自2014年2月至2015年12月在我院初治的127例AL(包括M15例,M244例,M324例,M47例,M519例,M64例,M72例;L11例,L220例,L31例)患者進(jìn)行檢測(cè)和動(dòng)態(tài)觀察WT1基因及幾種常見(jiàn)的標(biāo)志基因(BCR/ABL,PML/RARα,AML1/ETO,CBFβ/MYH11)在病程中的表達(dá)水平。比較急性髓性白血病(acute myeloid leukemia,AML)與急性淋巴細(xì)胞白血病(acute lymphoblastic leukemia,ALL)兩組中WT1基因表達(dá)的陽(yáng)性率,各組不同亞型之間WT1基因的表達(dá)水平,WT1基因表達(dá)的陽(yáng)性組與陰性組的第1次緩解(complete remission,CR)率,及分析WT1基因與常見(jiàn)標(biāo)志基因在不同病程階段中的相對(duì)表達(dá)水平的變化,判斷兩者間的關(guān)系。同時(shí)獨(dú)立探究初治WT1基因陽(yáng)性的患者在AML的不同疾病狀態(tài)下的表達(dá)水平,以作為MRD監(jiān)測(cè)的手段。結(jié)果:1.初治AL患者WT1基因表達(dá)的總陽(yáng)性率為81.1%(103/127),AML和A LL患者WT1基因表達(dá)的陽(yáng)性率分別為87.6%(92/105)、50%(11/22),兩者的中位表達(dá)水平分別為8.09、0.55,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2.AML各亞型(M1-M7)間WT1基因表達(dá)的陽(yáng)性率分別為M180%(4/5),M286.4%(38/44),M3100%(24/24),M471.4%(5/7),M584.2%(16/19),M675%(3/4),M7100%(2/2)。統(tǒng)計(jì)學(xué)無(wú)顯著性差異(P0.05)。WT1基因的中位表達(dá)水平分別為M18.18,M28.74,M318.88,M46.02,M53.54,M63.37,M74.44,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。3.AL患者中WT1基因表達(dá)陽(yáng)性組與陰性組第1次CR率分別為49.1%和58.8%,無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。4.在初治、緩解、未緩解、復(fù)發(fā)時(shí),WT1基因與常見(jiàn)標(biāo)志基因(BCR/ABL,AML1/ETO,CBFβ/MYH11)表達(dá)水平的變化具有相對(duì)一致性,統(tǒng)計(jì)學(xué)上無(wú)顯著性差異(P0.05)。5.獨(dú)立分析初治WT1基因陽(yáng)性的患者在AML不同疾病狀態(tài)下的表達(dá)水平,發(fā)現(xiàn)初治組(8.610)、未緩解組(11.690)、復(fù)發(fā)組(8.065)與緩解組(0.105)在WT1基因的表達(dá)水平上差異有顯著性(P0.05),但初治組(8.610)、未緩解組(11.690)、復(fù)發(fā)組(8.065)三者之間差異不明顯(P0.05)�？勺鳛橐环NMRD的監(jiān)測(cè)手段。結(jié)論:1.WT1基因在AL中高度表達(dá),且髓系表達(dá)高于淋巴系,但在兩者各自的亞型中,WT1基因的表達(dá)水平差異不大,結(jié)論尚需大樣本的臨床資料論證。2.初診時(shí)WT1基因的表達(dá)水平對(duì)AL的預(yù)后評(píng)價(jià)還有待進(jìn)一步大規(guī)模的臨床數(shù)據(jù)分析。3.在不同的病程階段中,WT1基因與常見(jiàn)標(biāo)志基因(BCR/ABL,AML1/ETO,CBFβ-MYH11)的表達(dá)水平的變化具有相對(duì)一致性,可作為臨床評(píng)估AL發(fā)生發(fā)展、及監(jiān)測(cè)MRD的指標(biāo)。
[Abstract]:Objective: to study the expression of WT1 gene in acute leukemia (AL) by retrospectively analyzing the clinical data of patients with acute leukemia (AL). The expression levels of WT1 gene and other marker genes were compared in order to judge the correlation between them. At the same time, it was minimal r esidual disease. Methods: the method of real-time fluorescence quantitative RT-PCR was used. From February 2014 to December 2015, 127 cases of ALL (including 15 cases of M244 and 324 cases of M324) were treated in our hospital. M72 cases; The WT1 gene and several common marker genes, BCR / ABL / ABL / RAR 偽 / AML1 / ETO, were detected and dynamically observed in patients with L11 / L220 / L31). The expression of CBF 尾 -MYH11 in the course of the disease was compared with that of acute myeloid leukemia in acute myeloid leukemia. The positive rate of WT1 gene expression in the two groups: acute lymphoblastic leukemia and acute lymphoblastic leukemia (ALL). The expression level of WT1 gene among different subtypes and the first remission rate of WT1 gene positive group and negative group. The changes of relative expression level of WT1 gene and common marker gene in different stages of disease course were analyzed. To determine the relationship between the two. At the same time, to explore the expression level of WT1 gene positive patients in different disease states of AML. Results: the total positive rate of WT1 gene expression in newly diagnosed AL patients was 81.1% and 103 / 127). The positive rates of WT1 gene expression in patients with AML and ALL were 87.6% and 92 / 105%, respectively. The median expression level of WT1 gene was 8.09, respectively. The positive rate of WT1 gene expression in M1-M7 subtypes of AML was 4 / 5 in M180g / M7, respectively. M286.4: 38 / 44 / M3100 / 24 / 24 / M471.4 / 5 / 7 / M584.22 / 16 / 19 / M675 / 4 / 4). There was no significant difference between M7100 and M7100. The median expression level of WT1 gene was M18.18m28.74m318.88, respectively. M46.02,M53.54,M63.37,M74.44. There was no significant difference in the rate of the first CR between the positive and negative groups of WT1 gene expression in AL patients (49.1% and 58.8%, respectively). There was no statistical difference between WT1 gene and common marker gene BCR / ABL AML1 / ETO at the time of initial treatment, remission, no remission and recurrence. The change of CBF 尾 -MYH11) expression level was relatively consistent. There was no statistically significant difference between the two groups (P0.05. 5. the expression level of WT1 gene positive patients in the first treatment group was independently analyzed under different disease states of AML, and it was found that the newly treated group was 8.610). There was a significant difference in the expression level of WT1 gene between non-remission group (11.690) and relapsed group (8.065) and remission group (0.105) (P0.05). However, the initial treatment group was 8.610m, and the non-remission group was 11.690). There was no significant difference among the recurrence group (8.065). It can be used as a monitoring method of MRD. Conclusion: 1. WT1 gene is highly expressed in AL. The expression of WT1 gene in medullary tissue was higher than that in lymphoid line, but there was no significant difference in the expression of WT1 gene between the two subtypes. Conclusion A large sample of clinical data is needed. 2. The prognostic evaluation of WT1 gene expression in patients with AL needs to be further analyzed on a large scale. 3. In different stages of disease course. The expression level of WT1 gene was consistent with that of BCR / ABL / AML1 / ETON CBF 尾 -MYH11. It can be used as a clinical index to evaluate the development of AL and to monitor MRD.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R733.71

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