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DNA methylation profiling of pediatric B-cell lymphoblastic leukemia with KMT2A rearrangement identifies hypomethylation at enhancer sites
Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, Campus Kiel,Schwanenweg 24, Kiel, Germany.;Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Pediat, Campus Kiel, Kiel, Germany..
Univ Barcelona, Inst Biomed August Pi Sunyer IDIBAPS, Dept Analomia Palol & Microbiol, Dept Farmacol & Microbiol, Barcelona, Spain..
Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Pediat, Campus Kiel, Kiel, Germany..
Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, Campus Kiel,Schwanenweg 24, Kiel, Germany..
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2017 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 64, no 3, article id e26251Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley , 2017. Vol. 64, no 3, article id e26251
Keywords [en]
acute lymphoblastic leukemia, DNA methylation, enhancer hypomethylation, infant ALL, KMT2A rearrangements
National Category
Medical Genetics Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-320291DOI: 10.1002/pbc.26251ISI: 000397225000013OAI: oai:DiVA.org:uu-320291DiVA, id: diva2:1090777
Funder
EU, FP7, Seventh Framework Programme, 282510Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2018-01-13Bibliographically approved

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Nordlund, Jessica

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