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PU.1 promotes cell cycle exit in the murine myeloid lineage associated with downregulation of E2F1.
- 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.)
- Subjects :
- Acute Disease
Animals
Animals, Newborn
Cell Cycle genetics
Cells, Cultured
Down-Regulation
Doxycycline pharmacology
E2F1 Transcription Factor genetics
Female
Immunoblotting
Interleukin Receptor Common gamma Subunit deficiency
Interleukin Receptor Common gamma Subunit genetics
Leukemia, Myeloid genetics
Leukemia, Myeloid metabolism
Leukemia, Myeloid pathology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Myeloid Cells drug effects
Myeloid Cells transplantation
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins deficiency
Proto-Oncogene Proteins genetics
Reverse Transcriptase Polymerase Chain Reaction
Spleen cytology
Spleen metabolism
Survival Analysis
Trans-Activators deficiency
Trans-Activators genetics
Transcriptome drug effects
Transcriptome genetics
Cell Cycle physiology
E2F1 Transcription Factor metabolism
Myeloid Cells metabolism
Proto-Oncogene Proteins physiology
Trans-Activators physiology
Subjects
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