UF Ematologia, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy.
Leuk Res. 2012 Oct;36(10):1290-5. doi: 10.1016/j.leukres.2012.05.023. Epub 2012 Jun 27.
We observed aberrant gene methylation of Wnt antagonists: sFRP1, sFRP2, sFRP4, sFRP5 and DKK1 in marrow cells of 55 MDS cases. Methylation of Wnt antagonist genes was associated with activation of the Wnt signaling pathway, consistent with the up-regulation of the Wnt downstream genes TCF1 and LEF1. Azacitidine exposure induced demethylation of Wnt-antagonist gene promoters and reduction of the non-phosphorylated β-catenin (NPBC) which is prevalent during Wnt pathway inactivation. Presence of ≥5% of bone marrow blasts was associated with methylation of sFRP1 and DKK1 and with methylation of more than two of the five Wnt antagonist genes.
我们观察到 55 例 MDS 病例骨髓细胞中 Wnt 拮抗剂基因的异常甲基化：sFRP1、sFRP2、sFRP4、sFRP5 和 DKK1。Wnt 拮抗剂基因的甲基化与 Wnt 信号通路的激活相关，这与 Wnt 下游基因 TCF1 和 LEF1 的上调一致。阿扎胞苷暴露诱导 Wnt 拮抗剂基因启动子去甲基化，并减少 Wnt 通路失活时普遍存在的非磷酸化β-连环蛋白（NPBC）。骨髓中 blast（原始细胞）≥5%与 sFRP1 和 DKK1 的甲基化以及五个 Wnt 拮抗剂基因中两个以上的甲基化相关。
