کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2136497 1087792 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
DNMT3A intragenic hypomethylation is associated with adverse prognosis in acute myeloid leukemia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
DNMT3A intragenic hypomethylation is associated with adverse prognosis in acute myeloid leukemia
چکیده انگلیسی


• Hypomethylation of DNMT3A in AML patients.
• Correlation between DNMT3A hypomethylation and parameters of AML.
• Association of DNMT3A hypomethylation with prognosis in AML.
• Association of DNMT3A hypomethylation with expression and mutation.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 39, Issue 10, October 2015, Pages 1041–1047
نویسندگان
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