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PU.1 promotes cell cycle exit in the murine myeloid lineage associated with downregulation of E2F1.

Authors :
Ziliotto R
Gruca MR
Podder S
Noel G
Ogle CK
Hess DA
DeKoter RP
Source :
Experimental hematology [Exp Hematol] 2014 Mar; Vol. 42 (3), pp. 204-217.e1. Date of Electronic Publication: 2013 Dec 05.
Publication Year :
2014

Abstract

Acute myeloid leukemia (AML) is characterized by increased proliferation and reduced differentiation of myeloid lineage cells. AML is frequently associated with mutations or chromosomal rearrangements involving transcription factors. PU.1 (encoded by Sfpi1) is an E26 transformation-specific family transcription factor that is required for myeloid differentiation. Reduced PU.1 levels, caused by either mutation or repression, are associated with human AML and are sufficient to cause AML in mice. The objective of this study was to determine whether reduced PU.1 expression induces deregulation of the cell cycle in the myeloid lineage. Our results showed that immature myeloid cells expressing reduced PU.1 levels (Sfpi1(BN/BN) myeloid cells) proliferated indefinitely in cell culture and expanded in vivo. Transplantation of Sfpi1(BN/BN) cells induced AML in recipient mice. Cultured Sfpi1(BN/BN) cells expressed elevated messenger RNA transcript and protein levels of E2F1, an important regulator of cell cycle entry. Restoration of PU.1 expression in Sfpi1(BN/BN) myeloid cells blocked proliferation, induced differentiation, and reduced E2F1 expression. Taken together, these data show that PU.1 controls cell cycle exit in the myeloid lineage associated with downregulation of E2F1 expression.<br /> (Copyright © 2014 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1873-2399
Volume :
42
Issue :
3
Database :
MEDLINE
Journal :
Experimental hematology
Publication Type :
Academic Journal
Accession number :
24316397
Full Text :
https://doi.org/10.1016/j.exphem.2013.11.011