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目的探讨WNT/β-catenin通路的关键抑制因子Dickkopf1(DKK-1)基因异常甲基化与急性白血病(AL)发病机制的相关性。方法采用逆转录聚合酶链式反应(RT-PCR)方法检测4个AL细胞系(NB4、Jurkat、Molt-4、CEM)、65例AL患者及20例正常对照骨髓单个核细胞中DKK-1基因mRNA的表达情况;采用甲基化特异性PCR(M SP)方法检测各标本及细胞系中DKK-1基因启动子区域的甲基化状态。结果与正常对照组比较,AL患者DKK-1基因mRNA表达量显著降低(P<0.05);正常对照组标本单个核细胞中不存在DKK-1基因的甲基化;DKK-1在AL患者中甲基化率为37.7%(24/65),其中急性淋巴细胞白血病(ALL)患者中甲基化率为41.2%(14/34),急性髄系白血病(AML)患者中甲基化率为28.6%(10/31)。结论 DKK-1甲基化及异常表达在急性白血病中是一种较为普遍的现象,其参与了部分急性白血病的发病过程。
Objective To investigate the relationship between abnormal methylation of Dickkopf1 (DKK-1) gene and the pathogenesis of acute leukemia (AL) in Wnt / β-catenin pathway. Methods DKK-1 was detected in 4 AL cell lines (NB4, Jurkat, Molt-4, CEM), 65 AL patients and 20 normal control bone marrow mononuclear cells by reverse transcription polymerase chain reaction The methylation status of DKK-1 gene promoter in each sample and cell line was detected by methylation-specific PCR (MSP). Results Compared with the normal control group, the mRNA expression of DKK-1 in AL patients was significantly decreased (P <0.05). There was no methylation of DKK-1 gene in the normal control group. DKK- The methylation rate was 37.7% (24/65). The methylation rate was 41.2% (14/34) in patients with acute lymphoblastic leukemia (ALL), and the methylation rate in patients with acute leukemia (AML) was 28.6% (10/31). Conclusion The methylation and abnormal expression of DKK-1 is a common phenomenon in acute leukemia, which is involved in the pathogenesis of some acute leukemia.