The Expression Of Survivin Gene In Leukemia Patients And Its Relationship With Promoter Methylation

Objective This study was aimed to explore the expression and clinical significance of survivin gene in leukemia patients and cell line, and to explore the relationship between the expression of survivin gene and promoter region methylation status. To make more explicit the mechanism of the expression and regulation of survivin gene,and to illuminate the role of survivin gene in pathogenesis, disease surveillance and treatment of leukaemia.Method The expression of survivin and casepase-3gene was detected by real-time qPCR in77acute leukemia patients,14CML patients and20non-hematopoietic malignancies patients. The relationship between expression of survivin gene and clinical parameters was analyzed. The expression of survivin gene before and after administration of cytarabine was detected in leukemia cell lines K562and ADM. The promoter methylation status of survivin gene was detected by methylation-specific PCR (MSP).Results1、The expression level of survivin in newly diagnosed AL was significantly higher than that in normal control (p＜0.05),while it decreased in complete remission(CR) patients.In relapsed patients,the expression of survivin increased again. The expression level of casepase-3was just the opposite. There was no difference of survivin and casepase-3expression between newly diagnosed and relapsed patients(p＞0.05).2、The expression level of survivin has no significant relationship with sex,age,fever, bleeding tendency, enlarged lymph nodes, WBC count, Hb and PLT count et al clinical parameters(p＞0.05). We found that survivin expression level correlated with classification of leukemia, CD34antigen and the percentage of blast cell in bone marrow (p＜0.05). The expression level of survivin and casepase-3related intimately with the stage of disease in CML(p＜0.05).3、The expression level of survivin was positively correlated with the percentage of blast cell in bone marrow(r=0.785, p＜0.001),While it was negatively correlated with the expression of caspase-3(r=-0.638, p＜0.001) 4、The detection result of methylation status of survivin promoter showed that the demethylation rate of survivin in de novo and relapsed group was both higher than that in normal control (p＜0.05), and the demethylation rate in de novo group was lower than that in relapsed group (p＜0.05). In addition, the expression level of survivin in methylation positive group was significantly lower than that in methylation negative group (p＜0.05). Besides,survivin expression was significantly negatively correlated with the methylation rate in AL patients.(r=-0.976, p=0.024)5、All the methylation detections of survivin gene were negative except the Ara-C24h group,control group in ADM cells and one control group in K562cells. There was no obvious difference of promoter methylation of survivin before and after administration of cytarabine (p＞0.05).Conclusions1、Abnormal expression of survivin may play an important role in initiation of leukemia, and it closely correlated with of relapse and prognosis of leukemia.2、Survivin may play a role of anti-apoptosis through inhibiting the transcription of apoptosis related protease. Over expression of survivin may be associated with leukemic hematopoiesis and malignant proliferation, and it would be served as a biological marker of poor prognosis in AL patients.3、Promoter methylation status of survivin gene is negatively correlated with gene expression, and it indicates that DNA methylation is one of the major methods of regulation of gene expression. It could influence the initiation and progression of disease through activating or silencing the expression of tumor-related genes.