title: DNA methylation profiling of pediatric B-cell lymphoblastic leukemia with KMT2A rearrangement identifies hypomethylation at enhancer sites.
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 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.
authors: Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.|Department of Pediatrics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Anke K
authors: AK
authors: Bergmann
authors: Departamento de Anatomía Patológica, Farmacología y Microbiología, Institutd'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors: Giancarlo
authors: G
authors: Castellano
authors: Department of Pediatrics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Julia
authors: J
authors: Alten
authors: Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Ole
authors: O
authors: Ammerpohl
authors: Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.|Institute of Human Genetics, University of Ulm & University Medical Center Ulm, Ulm, Germany.
authors: Julia
authors: J
authors: Kolarova
authors: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Sweden.
authors: Jessica
authors: J
authors: Nordlund
authors: Departamento de Anatomía Patológica, Farmacología y Microbiología, Institutd'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors: Jose Ignacio
authors: JI
authors: Martin-Subero
authors: Department of Pediatrics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Martin
authors: M
authors: Schrappe
authors: Institute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.|Institute of Human Genetics, University of Ulm & University Medical Center Ulm, Ulm, Germany.
authors: Reiner
authors: R
authors: Siebert
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
keywords: DNA methylation; KMT2A rearrangements; acute lymphoblastic leukemia; enhancer hypomethylation; infant ALL