Gebhard, Claudia and Glatz, Dagmar and Schwarzfischer, Lucia and Wimmer, Julia and Stasik, Sebastian and Nuetzel, Margit and Heudobler, Daniel and Andreesen, Reinhard and Ehninger, Gerhard and Thiede, Christian and Rehli, Michael (2019) Profiling of aberrant DNA methylation in acute myeloid leukemia reveals subclasses of CG-rich regions with epigenetic or genetic association. LEUKEMIA, 33 (1). pp. 26-36. ISSN 0887-6924, 1476-5551
Full text not available from this repository. (Request a copy)Abstract
Malignant transformation is frequently associated with disease-specific epigenetic alterations, but the underlying mechanisms and pathophysiological consequences remain poorly understood. Here, we used global comparative DNA methylation profiling at CG-rich regions of 27 acute myeloid leukemia (AML) samples to select a subset of aberrantly methylated CG-rich regions (similar to 400 regions, similar to 15,000 CpGs) for quantitative DNA methylation profiling in a large cohort of AML patients (n = 196) using MALDI-TOF analysis of bisulfite-treated DNA. Meta-analysis separated a subgroup of CG-rich regions showing highly correlated DNA methylation changes that were marked by histone H3 lysine 27 trimethylation in normal hematopoietic progenitor cells. While the group of non-polycomb group (PcG) target regions displayed methylation patterns that correlated well with molecular and cytogenetic markers, PcG target regions displayed a much weaker association with genetic features. However, the degree of methylation gain across the latter panel showed significant correlation with active DNMT3A levels and with overall survival. Our study suggests that both epigenetic as well as genetic aberrations underlay AML-related changes in DNA methylation at CG-rich regions and that the former may provide a marker to improve classification and prognostication of adult AML patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-SUPPRESSOR GENES; CEBPA MUTATIONS; PROGNOSTIC-SIGNIFICANCE; FUNDAMENTAL ROLE; CELL SIGNATURE; IDH2 MUTATIONS; ADULT PATIENTS; HYPERMETHYLATION; AML; POLYCOMB; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Apr 2020 07:55 |
| Last Modified: | 22 Apr 2020 07:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27927 |
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