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

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• 作者：Anke K. Bergmann ; Giancarlo Castellano ; Julia Alten ; Ole Ammerpohl ; Julia Kolarova ; Jessica Nordlund ; Jose Ignacio Martin-Subero ; Martin Schrappe and Reiner Siebert
• 刊名：Pediatric Blood & Cancer
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：64
• 期：3
• 全文大小：678K
• ISSN：1545-5017

文摘

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.