DNA methylation profiling of pediatric B-cell lymphoblastic leukemia with KMT2A rearrangement identifies hypomethylation at enhancer sites.
Pediatr Blood Cancer
; 64(3)2017 03.
Article
em En
| MEDLINE
| ID: mdl-27786413
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rearranjo Gênico
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Leucemia-Linfoma Linfoblástico de Células Precursoras B
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Biomarcadores Tumorais
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Histona-Lisina N-Metiltransferase
/
Metilação de DNA
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Perfilação da Expressão Gênica
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Proteína de Leucina Linfoide-Mieloide
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Female
/
Humans
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Infant
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Male
Idioma:
En
Revista:
Pediatr Blood Cancer
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha