MYST2 acetyltransferase expression and Histone H4 Lysine acetylation are suppressed in AML.
Exp Hematol
; 43(9): 794-802.e4, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-26072331
ABSTRACT
Chromatin-modifying enzymes are frequently altered in acute myeloid leukemia (AML). In the current study, we identified MYST2, a core histone acetyltransferase, to be suppressed in blast cells from AML patients compared with nonmalignant hematopoietic progenitor cells. Functionally, loss of MYST2 accelerated leukemic growth and colony formation, while forced expression of MYST2 induced H4K5 acetylation (H4K5Ac) and suppressed hematopoietic progenitor cell growth. Consistently, global H4K5Ac levels were frequently decreased in AML blasts. Low levels of H4K5Ac were most prominent in patients with complex karyotype AML and were associated with inferior overall survival in univariate but not multivariate analysis. ChIP-seq experiments in primary AML patients' blasts revealed widespread H4K5Ac deregulation, most prominent at gene promoters. Taken together, MYST2 is a repressed growth suppressor in AML mediating reduced acetylation of histone 4 at residue 5 and is associated with inferior AML patient survival.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Histonas
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Leucemia Mieloide Aguda
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Regulação Enzimológica da Expressão Gênica
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Regulação Leucêmica da Expressão Gênica
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Proteínas Supressoras de Tumor
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Histona Acetiltransferases
Limite:
Animals
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Humans
Idioma:
En
Revista:
Exp Hematol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha