Journal
PEDIATRIC BLOOD & CANCER
Volume 64, Issue 3, Pages -Publisher
WILEY
DOI: 10.1002/pbc.26251
Keywords
acute lymphoblastic leukemia; DNA methylation; enhancer hypomethylation; infant ALL; KMT2A rearrangements
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Funding
- European Union's Seventh Framework Program through the Blueprint Consortium [282510]
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Deregulation of the epigenome is an important pathogenetic mechanism in acute lymphoblastic leukemia (ALL) with lysine (K)-specific methyltransferase 2A rearrangement (KMT2Ar). We performed array-based DNA methylation profiling of KMT2Ar ALL cells from 26 children in comparison to normal B-cell precursors. Significant changes in DNA methylation in KMT2Ar ALL were identified in 2,545 CpG loci, influenced by age and the translocation partners AFF1 and MLLT1. In KMT2Ar ALL, DNA methylation loss was enriched at enhancers and for certain transcription factor binding sites such as BCL11A, EBF, and MEF2A. In summary, DNA methylation changes in KMT2Ar ALL target enhancers, genes involved in leukemogenesis and normal hematopoiesis, as well as transcription factor networks.
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