t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL.
Leuk Res
; 35(3): 305-9, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-20869771
ABSTRACT
The most frequent MLL-gene rearrangement found in leukemia is a reciprocal translocation with AF4 on chromosome 4 resulting in the formation of the MLL-AF4 and the AF4-MLL fusion genes. The oncogenic role of MLL-AF4 is documented but the significance of the reciprocal product - AF4-MLL in leukemia is less clear. In the human leukemia cell lines - RS4;11 and SEMK2-M1, both of which express MLL-AF4 and AF4-MLL, we knocked down the expression of AF4-MLL using siRNA. Loss of AF4-MLL had no effect on the growth of either RS4;11 or SEMK2-M1 cells. Furthermore, in SEMK2-M1 cells there were no changes in cell cycle or apoptosis with loss of AF4-MLL. In contrast, knockdown of MLL-AF4 significantly inhibited growth of both RS4;11 and SEMK2-M1. Additionally, in SEMK2-M1 cells, loss of MLL-AF4 led to G2/M cell cycle arrest and increased apoptosis. Overall, these results demonstrate that in t(4;11) leukemia, the MLL-AF4 fusion protein is critical for leukemia cell proliferation and survival while the AF4-MLL fusion product is dispensable.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Translocação Genética
/
Cromossomos Humanos Par 4
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Cromossomos Humanos Par 11
/
Proteínas Nucleares
/
Leucemia
/
Proteínas de Fusão Oncogênica
/
Apoptose
/
Proteínas de Ligação a DNA
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Proteína de Leucina Linfoide-Mieloide
Limite:
Humans
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos