DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Show full item record



Permalink

http://hdl.handle.net/10138/330863

Citation

Krali, O.; Palle, J.; Bäcklin, C.L.; Abrahamsson, J.; Norén-Nyström, U.; Hasle, H.; Jahnukainen, K.; Jónsson, Ó.G.; Hovland, R.; Lausen, B.; Larsson, R.; Palmqvist, L.; Staffas, A.; Zeller, B.; Nordlund, J. DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML). Genes 2021, 12, 895.

Title: DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)
Author: Krali, Olga; Palle, Josefine; Bäcklin, Christofer L.; Abrahamsson, Jonas; Norén-Nyström, Ulrika; Hasle, Henrik; Jahnukainen, Kirsi; Jónsson, Ólafur Gísli; Hovland, Randi; Lausen, Birgitte; Larsson, Rolf; Palmqvist, Lars; Staffas, Anna; Zeller, Bernward; Nordlund, Jessica
Publisher: Multidisciplinary Digital Publishing Institute
Date: 2021-06-10
URI: http://hdl.handle.net/10138/330863
Abstract: Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/<i>RUNX1-RUNX1T1</i>, normal karyotype, and <i>MLL/KMT2A</i>-rearranged subgroups (<i>p</i> &lt; 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML.


Files in this item

Total number of downloads: Loading...

Files Size Format View
genes-12-00895.pdf 5.546Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record