WT1基因在成人急性白血病中的临床研究

发布时间：2018-01-22 11:49

本文关键词： 急性白血病 WT1基因标志基因微小残留病　出处：《大连医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的:通过回顾分析初治急性白血病(acute leukemia,AL)患者的临床资料,研究WT1基因在AL分型中的表达特点;比较WT1基因与其他标志基因在病程阶段中表达水平的变化,以判断两者间的相关性;同时为白血病微小残留病(minimal r esidual disease,MRD)的监测提供参考意见。方法:采用荧光实时定量RT-PCR的方法,对自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)患者进行检测和动态观察WT1基因及几种常见的标志基因(BCR/ABL,PML/RARα,AML1/ETO,CBFβ/MYH11)在病程中的表达水平。比较急性髓性白血病(acute myeloid leukemia,AML)与急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)两组中WT1基因表达的阳性率,各组不同亚型之间WT1基因的表达水平,WT1基因表达的阳性组与阴性组的第1次缓解(complete remission,CR)率,及分析WT1基因与常见标志基因在不同病程阶段中的相对表达水平的变化,判断两者间的关系。同时独立探究初治WT1基因阳性的患者在AML的不同疾病状态下的表达水平,以作为MRD监测的手段。结果:1.初治AL患者WT1基因表达的总阳性率为81.1%(103/127),AML和A LL患者WT1基因表达的阳性率分别为87.6%(92/105)、50%(11/22),两者的中位表达水平分别为8.09、0.55,差异有统计学意义(P0.05)。2.AML各亚型(M1-M7)间WT1基因表达的阳性率分别为M180%(4/5),M286.4%(38/44),M3100%(24/24),M471.4%(5/7),M584.2%(16/19),M675%(3/4),M7100%(2/2)。统计学无显著性差异(P0.05)。WT1基因的中位表达水平分别为M18.18,M28.74,M318.88,M46.02,M53.54,M63.37,M74.44,差异无统计学意义(P0.05)。3.AL患者中WT1基因表达阳性组与阴性组第1次CR率分别为49.1%和58.8%,无统计学差异(P0.05)。4.在初治、缓解、未缓解、复发时,WT1基因与常见标志基因(BCR/ABL,AML1/ETO,CBFβ/MYH11)表达水平的变化具有相对一致性,统计学上无显著性差异(P0.05)。5.独立分析初治WT1基因阳性的患者在AML不同疾病状态下的表达水平,发现初治组(8.610)、未缓解组(11.690)、复发组(8.065)与缓解组(0.105)在WT1基因的表达水平上差异有显著性(P0.05),但初治组(8.610)、未缓解组(11.690)、复发组(8.065)三者之间差异不明显(P0.05)。可作为一种MRD的监测手段。结论:1.WT1基因在AL中高度表达,且髓系表达高于淋巴系,但在两者各自的亚型中,WT1基因的表达水平差异不大,结论尚需大样本的临床资料论证。2.初诊时WT1基因的表达水平对AL的预后评价还有待进一步大规模的临床数据分析。3.在不同的病程阶段中,WT1基因与常见标志基因(BCR/ABL,AML1/ETO,CBFβ-MYH11)的表达水平的变化具有相对一致性,可作为临床评估AL发生发展、及监测MRD的指标。
[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 伪 / 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.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R733.71

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