Gene-specific and global methylation patterns predict outcome in patients with acute myeloid leukemia
Gene-specific and global methylation patterns predict outcome in patients with acute myeloid leukemia
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DOI：
10.1038/leu.2010.41
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发表时间：
2010-05-01
期刊：
影响因子：
11.4
通讯作者：
Lehmann, S.
中科院分区：
文献类型：
--
作者：
Deneberg, S.;Grovdal, M.;Lehmann, S.
本研究旨在分析整体和基因特异性DNA甲基化模式对急性髓系白血病（AML）患者预后的影响。采用荧光甲基化分析法（LUMA）检测107例AML患者CDKN 2B（p15）、E-cadherin（CDH）和癌基因1（cancer 1）启动子甲基化及DNA甲基化水平，并进行细胞遗传学和分子突变学分析。此外，使用Illumina HumanMethylation 27阵列在一定比例的患者中评估全基因组启动子相关甲基化。在p15、CDH和p53 1的患者中分别发现66%、66%和51%的启动子甲基化。在多变量分析中，低总体DNA甲基化与较高的完全缓解率相关（风险比（HR）5.9，P=0.005），p15甲基化与较好的总体（HR 0.4，P=0.001）和无病生存率（HR 0.4，P=0.016）相关。CDH和CD 11甲基化与临床结果无关。突变状态和核型与基因特异性甲基化或整体甲基化无显著相关性。全基因组启动子相关甲基化的增加与更好的总体和无病生存以及LUMA低甲基化相关。我们的结论是，全球和基因特异性甲基化模式与AML患者的临床结果独立相关。Leukemia（2010）24，932-941; doi：10.1038/leu.2010.41; 2010年3月18日在线发表
This study was designed to analyze the effect of global and gene-specific DNA methylation patterns on the outcome of patients with acute myeloid leukemia (AML). Methylation of CDKN2B (p15), E-cadherin (CDH) and hypermethylated in cancer 1 (HIC1) promoters and global DNA methylation by luminometric methylation assay (LUMA) was analyzed in 107 AML patients and cytogenetic and molecular mutational analysis was performed. In addition, genome-wide promoter-associated methylation was assessed using the Illumina HumanMethylation27 array in a proportion of the patients. Promoter methylation was discovered in 66, 66 and 51% of the patients for p15, CDH and HIC1, respectively. In multivariate analysis, low global DNA methylation was associated with higher complete remission rate (hazard ratio (HR) 5.9, P=0.005) and p15 methylation was associated with better overall (HR 0.4, P=0.001) and disease-free survival (HR 0.4, P=0.016). CDH and HIC1 methylation were not associated with clinical outcome. Mutational status and karyotype were not significantly associated with gene-specific methylation or global methylation. Increased genome-wide promoter-associated methylation was associated with better overall and disease-free survival as well as with LUMA hypomethylation. We conclude that global and gene-specific methylation patterns are independently associated with the clinical outcome in AML patients. Leukemia (2010) 24, 932-941; doi:10.1038/leu.2010.41; published online 18 March 2010