DNA methylation profiling of pediatric B-cell lymphoblastic leukemia with KMT2A rearrangement identifies hypomethylation at enhancer sites.

Bergmann AK, Castellano G, Alten J, Ammerpohl O, Kolarova J, Nordlund J, Martin-Subero JI, Schrappe M, Siebert R

Pediatr Blood Cancer 64 (3) - [2017-03-00; online 2016-10-27]

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.

Bioinformatics Support for Computational Resources [Service]

NGI Uppsala (SNP&SEQ Technology Platform) [Technology development]

National Genomics Infrastructure [Technology development]

PubMed 27786413

DOI 10.1002/pbc.26251

Crossref 10.1002/pbc.26251