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目的研究Runx3基因启动子甲基化与儿童急性白血病(AL)的关系,探讨其在儿童AL发生发展中的生物学意义。方法82例白血病骨髓标本取自苏州大学附属儿童医院2005年1月至2007年2月收治的AL患儿,应用甲基化特异性聚合酶链反应(MSP)分析AL患儿和16例对照组儿童及白血病细胞株HL60、MOLT4、Jurkat、U937的Runx3基因甲基化状态,并用逆转录PCR(RT-PCR)方法检测各系Runx3基因的表达情况。结果对照组未检测检测到甲基化,而检测到该基因的表达;白血病细胞株均出现甲基化和非甲基化带,呈部分甲基化状态;82例AL患儿Runx3基因甲基化的出现率为39.0%,高于对照组,差异有统计学意义(P<0.05),其中急性淋巴细胞白血病(ALL)患儿为41.4%,急性髓系白血病(AML)患儿为33.3%,两者之间差异无统计学意义;存在Runx3启动子甲基化患儿首次化疗后完全缓解率低于未甲基化者,差异有统计学意义(P<0.05)。结论Runx3基因启动子甲基化在AL的发病机制中起一定的作用,其检测对估计白血病预后具有临床意义。
Objective To study the relationship between promoter methylation of Runx3 gene and childhood acute leukemia (AL) and explore its biological significance in the development of children with AL. Methods Eighty-two leukemia bone marrow samples were obtained from children with AL who were admitted to Children’s Hospital of Soochow University from January 2005 to February 2007 and were analyzed by methylation-specific polymerase chain reaction (MSP) in AL children and 16 controls Runx3 gene methylation status in children and leukemia cell lines HL60, MOLT4, Jurkat, U937 was detected. Runx3 gene expression in each line was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results In the control group, no methylation was detected and the expression of this gene was detected. Leukemic cell lines showed methylation and unmethylated status, and were partially methylated. Runx3 gene in 82 children with AL (39.0%), which was higher than that in the control group (P <0.05), of which 41.4% in children with acute lymphoblastic leukemia (ALL) and 33.3% in children with acute myeloid leukemia (AML) (P <0.05). There was no significant difference between the two groups. The complete remission rate was lower in patients with Runx3 promoter methylation than in those without methylation (P <0.05). Conclusion The promoter methylation of Runx3 gene plays a role in the pathogenesis of AL. The detection of Runx3 promoter methylation has a clinical significance in estimating the prognosis of leukemia.