Liu Feng-Zhi, Wang Ji-Shi, Zhu Hong-Qian
Department of Hematology, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou Province, China.
Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015 Aug;23(4):1190-3. doi: 10.7534/j.issn.1009-2137.2015.04.055.
A number of studies have demonstrated that the methylation of Dickkopf-1 (DKK1) gene promoter is related with the occurrence and development of many neoplastic diseases. By means of binding with corresponding receptors, DKK1 blocks the transduction pathway of Wnt/β-catenin/TCF and inhibits the proliferation and invasion of tumor cells, inducing apoptosis. Leukemia is a hyperplastic disease of hematopoietic stem cell malignant clone. Its pathogenesis has been confirmed to be closely related with the aberrant activation of Wnt signaling pathway. This pathway is associated with the self-renewal and proliferation of the hematopoietic stem cells, which can regulate growth, differentiation, migration of the cells, angiogenesis and embryonic development. Its expression is regulated by some suppressor genes like Dickkopf 1 (DKK1). Leukemia often accompanied by methylation modification of the DKK1 gene, so as to leads to silencing itself and activation of the Wnt signaling pathway, which cause the occurrence of leukemia. Some therapeutic methods on leukemia aiming at DKK1 gene have been reported, among which DKK1 gene was demethylated. The intensive study on the expression and function of DKK1 should be important for the early diagnosis, treatment and prognosis. This article reviews the current progress in this field.
多项研究表明，Dickkopf-1（DKK1）基因启动子的甲基化与多种肿瘤性疾病的发生发展相关。通过与相应受体结合，DKK1阻断Wnt/β-连环蛋白/TCF转导通路，抑制肿瘤细胞的增殖和侵袭，诱导细胞凋亡。白血病是造血干细胞恶性克隆的增生性疾病。其发病机制已被证实与Wnt信号通路的异常激活密切相关。该通路与造血干细胞的自我更新和增殖相关，可调节细胞的生长、分化、迁移、血管生成及胚胎发育。其表达受Dickkopf 1（DKK1）等一些抑制基因调控。白血病常伴有DKK1基因的甲基化修饰，从而导致其自身沉默及Wnt信号通路激活，引发白血病的发生。已有一些针对DKK1基因的白血病治疗方法被报道，其中包括使DKK1基因去甲基化。深入研究DKK1的表达及功能对白血病的早期诊断、治疗及预后具有重要意义。本文综述了该领域的研究进展。
