The MYB proto-oncogene suppresses monocytic differentiation of acute myeloid leukemia cells via transcriptional activation of its target gene GFI1

Zhao, L., Ye, P. and Gonda, T. J. (2014) The MYB proto-oncogene suppresses monocytic differentiation of acute myeloid leukemia cells via transcriptional activation of its target gene GFI1. Oncogene, 33 35: 4442-4449. doi:10.1038/onc.2013.419


Author Zhao, L.
Ye, P.
Gonda, T. J.
Title The MYB proto-oncogene suppresses monocytic differentiation of acute myeloid leukemia cells via transcriptional activation of its target gene GFI1
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1038/onc.2013.419
Open Access Status Not yet assessed
Volume 33
Issue 35
Start page 4442
End page 4449
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing
Language eng
Abstract The MYB gene is a master regulator of hematopoiesis and contributes to leukemogenesis in several species including humans. Although it is clear that MYB can promote proliferation, suppress apoptosis and block differentiation, the identities of the MYB target genes that mediate these effects have only been partially elucidated. Several studies, including our own, have collectively identified substantial numbers of MYB target genes, including candidates for each of these activities; however, functional validation, particularly in the case of differentiation suppression, has lagged well behind. Here we show that GFI1, which encodes an important regulator of hematopoietic stem cell (HSC) function and granulocytic differentiation, is a direct target of MYB in myeloid leukemia cells. Chromatin immunoprecipitation and reporter studies identified a functional MYB-binding site in the promoter region of GFI, whereas ectopic expression and small hairpin RNA-mediated knockdown of MYB resulted in concomitant increases and decreases, respectively, in GFI1 expression. We also demonstrate that GFI1, like MYB, can block the induced monocytic differentiation of a human acute myeloid leukemia cell line, and most importantly, that GFI1 is essential for MYB's ability to block monocytic differentiation. Thus, we have identified a target of MYB that is a likely mediator of its myeloid differentiation-blocking activity, and which may also be involved in MYB's activities in regulating normal HSC function and myeloid differentiation.
Keyword U937
MYB
GFI1
Monocytic differentiation
Target gene
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication 14 October 2013

 
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Created: Sat, 15 Mar 2014, 00:40:46 EST by Kylie Hengst on behalf of UQ Diamantina Institute