RUNX1 meets MLL: epigenetic regulation of hematopoiesis by two leukemia genes.
Leukemia
; 27(9): 1793-802, 2013 Sep.
Article
en En
| MEDLINE
| ID: mdl-23817177
ABSTRACT
A broad range of human leukemias carries RUNX1 and MLL genetic alterations. Despite such widespread involvements, the relationship between RUNX1 and MLL has never been appreciated. Recently, we showed that RUNX1 physically and functionally interacts with MLL, thereby regulating the epigenetic status of critical cis-regulatory elements for hematopoietic genes. This newly unveiled interaction between the two most prevalent leukemia genes has solved a long-standing conundrum leukemia-associated RUNX1 N-terminal point mutants that exhibit no obvious functional abnormalities in classical assays for the assessment of transcriptional activities. These mutants turned out to be defective in MLL interaction and subsequent epigenetic modifications that can be examined by the histone-modification status of cis-regulatory elements in the target genes. RUNX1/MLL binding confirms the importance of RUNX1 function as an epigenetic regulator. Recent studies employing next-generation sequencing on human hematological malignancies identified a plethora of mutations in epigenetic regulator genes. These new findings would enhance our understanding on the mechanistic basis for leukemia development and may provide a novel direction for therapeutic applications. This review summarizes the current knowledge about the epigenetic regulation of normal and malignant hematopoiesis by RUNX1 and MLL.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia
/
Regulación Leucémica de la Expresión Génica
/
Epigénesis Genética
/
Proteína de la Leucemia Mieloide-Linfoide
/
Subunidad alfa 2 del Factor de Unión al Sitio Principal
/
Hematopoyesis
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Leukemia
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2013
Tipo del documento:
Article
País de afiliación:
Singapur