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.
- Bergmann, A. K.
- Castellano, G.
- Alten, J.
- Ammerpohl, O.
- Kolarova, J.
- Nordlund, J.
- Martin-Subero, J. I.
- Schrappe, M.
- Siebert, R.
Keywords
- B-Lymphocytes/metabolism
- Biomarkers, Tumor/*genetics
- Case-Control Studies
- Comparative Genomic Hybridization
- *DNA Methylation
- Female
- Follow-Up Studies
- *Gene Expression Profiling
- *Gene Rearrangement
- Histone-Lysine N-Methyltransferase/*genetics
- Humans
- Infant
- Male
- Myeloid-Lymphoid Leukemia Protein/*genetics
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology
- Prognosis
- Promoter Regions, Genetic/genetics
- DNA methylation
- KMT2A rearrangements
- acute lymphoblastic leukemia
- enhancer hypomethylation
- infant ALL
