Deregulated expression of Kruppel-like factors in acute myeloid leukemia.
Leuk Res
; 35(7): 909-13, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21470678
ABSTRACT
The known participation of Kruppel-like transcription factors (KLF) in cellular differentiation prompted us to investigate their expression in acute myeloid leukemia (AML) blast cells that are typically blocked in their differentiation. We determined the expression patterns of KLFs with a putative role in myeloid differentiation in a large cohort of primary AML patient samples, CD34+ progenitor cells and granulocytes from healthy donors. We found that KLF2, KLF3, KLF5 and KLF6 are significantly lower expressed in AML blast and CD34+ progenitor cells as compared to normal granulocytes. Moreover, we found markedly increased KLF levels in acute promyelocytic leukemia patients who received oral ATRA. Accordingly, we observed a strong induction of KLF5/6 upon ATRA-treatment in NB4 and HT93 APL but not in ATRA-resistant NB4-R cells. Lastly, knocking down KLF5 or KLF6 in NB4 cells significantly attenuated neutrophil differentiation. In conclusion, we found a significant repression of KLF transcription factors in primary AML samples as compared to mature neutrophils and further show that KLF5 and KLF6 are functionally involved in neutrophil differentiation of APL cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
/
Proteínas Proto-Oncogênicas
/
Fatores de Transcrição Kruppel-Like
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Suíça