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

Olga Krali, Josefine Palle, Christofer L Bäcklin, Jonas Abrahamsson, Ulrika Norén-Nyström, Henrik Hasle, Kirsi Jahnukainen, Ólafur Gísli Jónsson, Randi Hovland, Birgitte Lausen, Rolf Larsson, Lars Palmqvist, Anna Staffas, Bernward Zeller, Jessica Nordlund

Research output: Contribution to journalArticlepeer-review

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)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML.
Original languageEnglish
JournalGenes
Volume12
Issue number6
DOIs
Publication statusPublished - 10 Jun 2021

Other keywords

  • 450k array
  • DNA methylation
  • acute myeloid leukemia
  • classification
  • epigenetics
  • pediatric AML
  • subtyping
  • Leukemia, Myeloid, Acute

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