ArticleClinical epigenetics2022
A validation study of potential prognostic DNA methylation biomarkers in patients with acute myeloid leukemia using a custom DNA methylation sequencing panel.
Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Identification of DNA methylation biomarkers in amniotic fluid for prenatal detection of congenital heart disease (CHD).Clinical epigenetics · 2026Article
- Epigenomic diagnosis and prognosis of Acute Myeloid Leukemia.Nature communications · 2025Article
- Identification of an Ara-C resistance-related gene risk score and the role of S100A4 in AML via NR6A1-dependent activation and p53 regulation.Frontiers in pharmacology · 2025Article
- Clinical promise and applications of epigenetic biomarkers.Clinical epigenetics · 2024Article
- CEBPA mutations in acute myeloid leukemia: implications in risk stratification and treatment.International journal of hematology · 2024Review
- MethScore as a new comprehensive DNA methylation-based value refining the prognosis in acute myeloid leukemia.Clinical epigenetics · 2024Article
- DNA methylation inhibitors adverse reaction characteristic analysis: an analysis based on the European spontaneous adverse event reporting system.Frontiers in pharmacology · 2024Article
- Targeting DNA Methylation in Leukemia, Myelodysplastic Syndrome, and Lymphoma: A Potential Diagnostic, Prognostic, and Therapeutic Tool.International journal of molecular sciences · 2022Review
- SLC22A3 methylation-mediated gene silencing predicts adverse prognosis in acute myeloid leukemia.Clinical epigenetics · 2022Article
- Role of Biomarkers in the Management of Acute Myeloid Leukemia.International journal of molecular sciences · 2022Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMultiple studies have reported the prognostic impact of DNA methylation changes in acute myeloid leukemia (AML). However, these epigenetic markers have not been thoroughly validated and therefore are still not considered in clinical practice. Hence, we aimed to independently verify results of selected studies describing the relationship between DNA methylation of specific genes and their prognostic potential in predicting overall survival (OS) and event-free survival (EFS).
resultsFourteen studies (published 2011-2019) comprising of 27 genes were subjected to validation by a custom NGS-based sequencing panel in 178 newly diagnosed non-M3 AML patients treated by 3 + 7 induction regimen. The results were considered as successfully validated, if both the log-rank test and multivariate Cox regression analysis had a p-value ≤ 0.05. The predictive role of DNA methylation was confirmed for three studies comprising of four genes: CEBPA (OS: p = 0.02; EFS: p = 0.03), PBX3 (EFS: p = 0.01), LZTS2 (OS: p = 0.05; EFS: p = 0.0003), and NR6A1 (OS: p = 0.004; EFS: p = 0.0003). For all of these genes, higher methylation was an indicator of longer survival. Concurrent higher methylation of both LZTS2 and NR6A1 was highly significant for survival in cytogenetically normal (CN) AML group (OS: p < 0.0001; EFS: p < 0.0001) as well as for the whole AML cohort (OS: p = 0.01; EFS < 0.0001). In contrast, for two studies reporting the poor prognostic effect of higher GPX3 and DLX4 methylation, we found the exact opposite, again linking higher GPX3 (OS: p = 0.006; EFS: p < 0.0001) and DLX4 (OS: p = 0.03; EFS = 0.03) methylation to a favorable treatment outcome. Individual gene significance levels refer to the outcomes of multivariate Cox regression analysis.
conclusionsOut of twenty-seven genes subjected to DNA methylation validation, a prognostic role was observed for six genes. Therefore, independent validation studies are necessary to reveal truly prognostic DNA methylation changes and to enable the introduction of these promising epigenetic markers into clinical practice.
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