Department of Hematology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Leuk Res. 2011 Apr;35(4):516-21. doi: 10.1016/j.leukres.2010.08.002. Epub 2010 Sep 9.
We performed methylation specific PCR analysis on the RIZ1 promoter in MDS and AML. Methylation was detected in 17 of 34 MDS (50%) and 22 of 72 AML (31%) (p=0.053). Methylation was detected in eleven of 17 secondary AML from MDS (65%), and eleven of 55 de novo AML (20%) (p=0.0005). Bisulfite sequence revealed methylation at many CpG sites in the promoter. Decreased RIZ1 expression was accompanied by methylation in six of nine samples examined, while it was also observed in seven of 13 without methylation. Treatment of AML cells, that have RIZ1 methylation, with 5-Aza-dC, induced growth suppression with RIZ1 restoration. Our results suggest that the RIZ1 gene is inactivated in MDS and AML in part by methylation, whereas another mechanism should be involved in others.
我们在 MDS 和 AML 中对 RIZ1 启动子进行了甲基化特异性 PCR 分析。在 34 例 MDS 中有 17 例（50%）和 72 例 AML 中有 22 例（31%）检测到甲基化（p=0.053）。在 17 例 MDS 继发的 AML 中有 11 例（65%）和 55 例初发 AML 中有 11 例（20%）检测到甲基化（p=0.0005）。亚硫酸氢盐测序显示启动子中有许多 CpG 位点发生甲基化。在检测的 9 个样本中有 6 个伴随甲基化出现了 RIZ1 表达降低，而在 13 个没有甲基化的样本中也观察到了这种情况。用 5-Aza-dC 处理有 RIZ1 甲基化的 AML 细胞，诱导生长抑制并恢复 RIZ1 表达。我们的结果表明，RIZ1 基因在 MDS 和 AML 中部分通过甲基化失活，而其他机制可能涉及其他原因。
