急性髓系白血病患者骨髓中WT1基因的表达及其对预后的影响和意义

发布时间：2018-03-04 08:31

本文选题：急性髓系白血病　切入点：WT1基因　出处：《安徽医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的研究急性髓系白血病(AML)患者骨髓中WT1基因的表达并探讨WT1基因的表达水平对疗效及预后的影响和意义。方法1.采用实时荧光定量PCR法检测75例初诊AML患者(非APL)治疗各阶段骨髓WT1基因、内参因子(GADPH)及其他相关基因的拷贝数,染色体的检测采用R显带法。以NQ比值=WT1基因拷贝数/内参基因拷贝数来计算WT1表达水平,分析WT1基因的表达水平与相关的临床参数及危险因素的关系。2.将所有患者据WT1基因表达水平的不同分为WT1高表达组及低表达组,比较两组患者诱导化疗后的完全缓解(CR)率、1年内复发率及死亡率、2年总生存率(OS)及无事件生存率(EFS)的差别,并分析治疗中WT1基因表达水平的变化与2年OS的关系。结果75例初诊AML患者WT1基因表达阳性率为98.7%;初诊时WT1基因表达水平的高低与年龄、性别、FAB分型及预后分组等情况无相关性(P0.05)。WT1基因的表达水平与AML1/ETO融合基因阳性表达水平呈正相关(P0.05)。不同危险分组,高危组中WT1高表达人数的比例明显高于低危组(P0.05)。初诊组、复发组及未缓解组患者WT1基因的中位表达水平两两比较均无统计学意义(P0.05),但分别与缓解组比较时差异均显著(P0.05);复发前组分别与缓解组、复发组患者WT1中位表达水平比较,差异均有统计学意义(P0.05)。初诊时WT1高表达组患者的CR率为65.4%(17/26),低表达组为93.9%(46/49),两组比较统计学差异显著(P=0.004);两组患者1年内的死亡率高表达组高于低表达组(P0.05),但复发率无统计学差别;两组患者2年总生存与无事件生存曲线差异均有统计学意义(P0.05),高表达组OS及EFS率均明显低于低表达组。治疗后约1个月、3个月及6个月时患者WT1基因的表达水平较初诊时下降1个数量级以上的,其患者两年总生存率相对较高(P0.05)。结论:1.WT1基因在AML患者骨髓中表达阳性率很高,且在疾病进展及治疗不同时期呈动态变化,因此有助疾病的诊断及可用于AML患者微小残留病变(MRD)的监测。2.WT1基因高表达组CR率及生存率均低于低表达组,因此WT1基因可作为评估AML患者(非APL)疗效及预后的有效指标。3.治疗中WT1表达水平变化的监测有助于评价预后及指导治疗。
[Abstract]:Objective to study the expression of WT1 gene in bone marrow of patients with acute myeloid leukemia (AMLL) and to explore the effect and significance of WT1 gene expression on the curative effect and prognosis. Non APL) treatment of bone marrow WT1 gene, The number of copies of GADPHand other related genes was detected by R-banding method. The expression level of WT1 was calculated by using the NQ ratio of WT1 gene copy number / internal reference gene copy number. To analyze the relationship between the expression level of WT1 gene and related clinical parameters and risk factors. All the patients were divided into high expression group and low expression group according to the different expression level of WT1 gene. The difference of complete remission (CR) rate, recurrence rate and mortality rate, 2-year survival rate (OS) and event free survival rate (EFS) between the two groups after induced chemotherapy were compared. Results the positive rate of WT1 gene expression in 75 newly diagnosed AML patients was 98.7. There was no correlation between the expression level of AML1/ETO fusion gene and the expression level of AML1/ETO fusion gene. In different risk groups, the proportion of high expression of WT1 in high risk group was significantly higher than that in low risk group (P 0. 05), the expression level of WT1 gene was positively correlated with the positive expression level of AML1/ETO fusion gene. The proportion of high expression of WT1 in high risk group was significantly higher than that in low risk group (P 0. 05). There was no significant difference in the median expression level of WT1 gene between the relapsing group and the non-remission group, but there was significant difference between the two groups in comparison with the remission group (P 0.05), and the median expression level of WT1 between the pre relapse group and the remission group and the relapse group was significantly higher than that of the control group. The CR rate of the patients with high expression of WT1 was 65.44 / 26%, and that of the group with low expression was 93.9 / 46 / 49, the difference between the two groups was statistically significant (P 0.05). The mortality rate of high expression group in one year was higher than that of low expression group (P 0.05), but the recurrence rate had no statistical difference. The difference of survival curve between two groups was statistically significant (P 0.05). The rates of OS and EFS in high expression group were significantly lower than those in low expression group. The expression level of WT1 gene was about 1 month, 3 months and 6 months after treatment. More than one order of magnitude lower than at first visit, Conclusion: 1. The positive rate of WT1 gene expression in bone marrow of AML patients is very high, and it changes dynamically at different stages of disease progression and treatment. Therefore, the CR rate and survival rate of patients with high expression of WT1 gene were lower than those of patients with low expression of WT1 gene. Therefore, WT1 gene can be used as an effective index to evaluate the curative effect and prognosis of AML patients. 3. Monitoring the changes of WT1 expression during treatment is helpful to evaluate the prognosis and guide the treatment.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R733.71

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