Preferential hypermethylation of the Dickkopf-1 promoter in core-binding factor leukaemia
Preferential hypermethylation of the Dickkopf-1 promoter in core-binding factor leukaemia
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DOI：
10.1111/j.1365-2141.2007.06702.x
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发表时间：
2007-09-01
影响因子：
6.5
通讯作者：
Ando, Kiyoshi
中科院分区：
文献类型：
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作者：
Suzuki, Rikio;Onizuka, Makoto;Ando, Kiyoshi
Dickkopf-1（DKK 1）基因产物是细胞外Wnt抑制剂。DKK 1启动子的超甲基化导致转录沉默，并可能在癌症发展中发挥重要作用。在这里，我们研究了急性髓系白血病（AML），特别是核心结合因子（CBF）白血病患者DKK 1启动子的超甲基化。应用甲基化特异性聚合酶链反应（methylation-specific polymerase chain reaction，PCR）技术检测47例AML患者DKK 1基因甲基化状态。14例（29.8%）患者中发现DKK 1甲基化，CBF白血病患者（12例患者中的6例）的DKK 1甲基化频率高于急性早幼粒细胞白血病（APL）患者（6例患者中的0例）（P = 0.03）。与此相反，Wnt抑制因子-1甲基化在APL（6例患者中的4例）中发现，但在CBF白血病（12例患者中的0例）中未发现（P = 0.001）。多变量分析表明，DKK 1甲基化是总生存率较差的危险因素。使用在诊断和复发时获得的四对样本进行的序列分析表明，DKK 1甲基化参与了白血病的进展。因此，DKK 1甲基化可能参与白血病的发生，特别是在CBF白血病中，并且可能是AML中有用的预后标志物。
The Dickkopf-1 (DKK1) gene product is an extracellular Wnt inhibitor. Hypermethylation of the DKK1 promoter results in transcriptional silencing and may play an important role in cancer development. Here, we investigated hypermethylation of the DKK1 promoter in patients with acute myeloid leukaemia (AML), especially core-binding factor (CBF) leukaemia. The methylation status of DKK1 was analysed using methylation-specific polymerase chain reaction in 47 patients with AML. DKK1 methylation was found in 14 (29.8%) patients, and more frequently in those with CBF leukaemia (6 of 12 patients), than in those with acute promyelocytic leukaemia (APL) (0 of 6 patients) (P = 0.03). In contrast, Wnt inhibitory factor-1 methylation was found in APL (4 of 6 patients) but not in CBF leukaemia (0 of 12 patients) (P = 0.001). Multivariate analyses suggested that DKK1 methylation was a risk factor for poorer overall survival. Sequential analysis using four paired samples obtained at diagnosis and relapse suggested that DKK1 methylation was involved in the progression of leukaemia. Therefore, DKK1 methylation may be involved in leukaemogenesis, especially in CBF leukaemia, and may be a useful prognostic marker in AML.