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Title 

Regulation of HOXA9 activity by predominant expression of DACH1 against C/EBPα and GATA-1 in myeloid leukemia with MLL-AF9

Authors 

J W LeeH S KimJ HwangY H KimG Y LimW J SohnSuk Ran YoonJ Y KimT S ParkS H OhK M ParkS U ChoiZ Y RyooS Lee

Publisher 

Elsevier

Issue Date 

2012

Citation 

Biochemical and Biophysical Research Communications, vol. 426, no. 3, pp. 299-305

Keywords 

C/EBPαDACH1GATA-1HOXA9MEIS1MLL-AF9

Abstract 

Although MLL-AF9 caused by the chromosomal translocation t(9; 11) has a critical role in acute myeloid leukemia, the molecular pathogenesis is poorly understood. Here, we identified that the cell fate determination factor DACH1 is directly up-regulated by MLL-AF9. Recently we showed that the forced expression of DACH1 in myeloid cells induced p27. Kip1 and repressed p21. Cip1, which is a pivotal characteristic of the myeloid progenitor. Consistent with our previous study, ectopic expression of DACH1 contributed to the maintenance of colonogenic activity and blocked the differentiation of myeloid progenitors. Moreover, we here identified an endogenous HOXA9-DACH1 complex mediated by the carboxyl terminus of DACH1 in t(9; 11) leukemia cells. qRT-PCR revealed that DACH1 has a stronger transcription-promoting activity with HOXA9 than does PBX2 with HOXA9. Furthermore, C/EBPα and GATA-1 can directly bind to the promoter of DACH1 and act as a transcriptional suppressor. Expression of DACH1 is down-regulated during myeloid differentiation and shows an inverse pattern compared to C/EBPα and GATA-1 expression. However, ectopic expression of C/EBPα and/or GATA-1 could not abrogate the over-expression of DACH1 induced by MLL-AF9. Therefore, we postulate that the inability of C/EBPα and GATA-1 to down-regulate DACH1 expression induced by MLL-AF9 during myeloid differentiation may contribute to t(9; 11) leukemogenesis.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2012.08.048

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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