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

2016; Wiley; Volume: 64; Issue: 3 Linguagem: Inglês

10.1002/pbc.26251

1545-5017

Anke Bergmann, Giancarlo Castellano, Julia Alten, Ole Ammerpohl, Julia Kolarova, Jessica Nordlund, José I. Martín‐Subero, Martin Schrappe, Reiner Siebert,

Genetic Syndromes and Imprinting

Abstract 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 KMT2A r ALL cells from 26 children in comparison to normal B‐cell precursors. Significant changes in DNA methylation in KMT2A r ALL were identified in 2,545 CpG loci, influenced by age and the translocation partners AFF1 and MLLT1 . In KMT2A r 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 KMT2A r ALL target enhancers, genes involved in leukemogenesis and normal hematopoiesis, as well as transcription factor networks.