Zhang Ying-ying, Yao Dong-ming, Zhu Xiao-wen, Zhou Jing-dong, Ma Ji-chun, Yang Jing, Wen Xiang-mei, Guo Hong, Lin Jiang, Qian Jun
Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
Leuk Res. 2015 Oct;39(10):1041-7. doi: 10.1016/j.leukres.2015.06.015. Epub 2015 Jul 6.
DNA methyltransferase 3A (DNMT3A), a member of de novo methyltransferases, has been found with overexpression in several cancers including acute myeloid leukemia (AML). The present study was aimed to investigate the methylation status of DNMT3A intragenic differentially methylated region 2 (DMR2) using real-time quantitative methylation-specific PCR (RQ-MSP) and analyze its clinical significance in AML. Aberrant hypomethylation of DNMT3A gene was found in 55.3% (84/152) of AML cases, but the status of DNMT3A hypomethylation was not correlated with the expression of four DNMT3A isoforms as well as DNMT3A mutation. There was no significant difference in the rates of complete remission (CR) between patients with and without DNMT3A hypomethylation. However, the patients with DNMT3A hypomethylation had shorter overall survival (OS) time than those without DNMT3A hypomethylation (7 months vs. 11 months, P=0.034). Moreover, the patients with DNMT3A hypomethylation also showed significantly shorter OS than those without DNMT3A hypomethylation in cytogenetically normal AML (CN-AML) (7 months vs. 25 months, P=0.011). Multivariate analysis confirmed the independent adverse impact of DNMT3A hypomethylation in CN-AML. Our data suggest that DNMT3A DMR2 hypomethylation is a negative prognostic hallmark in CN-AML.
DNA甲基转移酶3A（DNMT3A）是一种从头甲基转移酶，已发现在包括急性髓系白血病（AML）在内的多种癌症中过表达。本研究旨在使用实时定量甲基化特异性PCR（RQ-MSP）研究DNMT3A基因内差异甲基化区域2（DMR2）的甲基化状态，并分析其在AML中的临床意义。在55.3%（84/152）的AML病例中发现了DNMT3A基因的异常低甲基化，但DNMT3A低甲基化状态与四种DNMT3A异构体的表达以及DNMT3A突变均无相关性。DNMT3A低甲基化患者与未发生DNMT3A低甲基化患者的完全缓解（CR）率无显著差异。然而，DNMT3A低甲基化患者的总生存期（OS）比未发生DNMT3A低甲基化患者短（7个月对11个月，P=0.034）。此外，在细胞遗传学正常的AML（CN-AML）中，DNMT3A低甲基化患者的OS也显著短于未发生DNMT3A低甲基化患者（7个月对25个月，P=0.011）。多因素分析证实了DNMT3A低甲基化在CN-AML中的独立不良影响。我们的数据表明，DNMT3A DMR2低甲基化是CN-AML的一个不良预后标志。
