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• W3014808627 abstract "DNMT3A mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. CDKN2B plays an important role in the regulation of hematopoietic progenitor cells and DNMT3A mutation is associated with CDKN2B promoter methylation. We analyzed the characteristics of DNMT3A mutations including their clinical significance in AML and their influence on promoter methylation and CDKN2B expression.A total of 142 adults, recently diagnosed with de novo AML, were enrolled in the study. Mutations in DNMT3A, CEBPA, and NPM1 were analyzed by bidirectional Sanger sequencing. We evaluated CDKN2B promoter methylation and expression using pyrosequencing and RT-qPCR.We identified DNMT3A mutations in 19.7% (N=28) of enrolled patients with AML, which increased to 29.5% when analysis was restricted to cytogenetically normal-AML. Mutations were located on exons from 8-23, and the majority, including R882, were found to be present on exon 23. We also identified a novel frameshift mutation, c.1590delC, in AML with biallelic mutation of CEBPA. There was no significant difference in CDKN2B promoter methylation according to the presence or type of DNMT3A mutations. CDKN2B expression inversely correlated with CDKN2B promoter methylation and was significantly higher in AML with R882H mutation in DNMT3A. We demonstrated that DNMT3A mutation was associated with poor AML outcomes, especially in cytogenetically normal-AML. The DNMT3A mutation remained as the independent unfavorable prognostic factor after multivariate analysis.We characterized DNMT3A mutations in AML and revealed the association between the DNMT3A mutation and CDKN2B expression and clinical outcome." @default.
• W3014808627 created "2020-04-10" @default.
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• W3014808627 date "2020-03-31" @default.
• W3014808627 modified "2023-10-06" @default.
• W3014808627 title "Characteristics of<i>DNMT3A</i>mutations in acute myeloid leukemia" @default.
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• W3014808627 doi "https://doi.org/10.5045/br.2020.55.1.17" @default.
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