Is PU.1 a dosage-sensitive regulator of haemopoietic lineage commitment and leukaemogenesis?
Abstract
The transcription factor PU.1 is an essential regulator of haemopoiesis and a suppressor of myeloid leukaemia. PU.1 displays a complex expression pattern characterized by high expression in myeloid cells and low amounts in lymphoid cells. Based on this transcriptional profile, and the analysis of cell lines and mice expressing altered levels of PU.1, a model has been proposed where the concentration of PU.1 determines cell fate, whereas the graded reduction, but not absence, of PU.1 facilitates leukaemogenesis. The recent reports of mouse strains that enable the accurate determination of PU.1 expression and the conditional inactivation of PU.1 in adult haemopoiesis have led us to re-examine our understanding of the complex functions of PU.1. Here, we will discuss the data that, we believe, argue against the dosage-sensitive model of PU.1-mediated lineage commitment and leukaemogenesis.
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PU.1 regulates lineage-specific gene expression in a dose-dependent manner.
“PU.1 regulates lineage-specific gene expression in a dose-dependent manner21–23.”
From Lymphoid gene expression supports neuroprotective microglia function (2025) · cites this paper as [23]
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- Authors
- Dakic, A., Wu, L., & Nutt, S. L.
- Affiliations
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Corresponding author
- Nutt, Stephen L.
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 28
- Issue
- 3
- Pages
- 108-114
- ISSN
- 1471-4906 (ISSN-L)
- OpenAlex
- W1963771050
- Cited by
- 72
- References
- 16
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 10
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer Australia
- National Health and Medical Research Council
- Cancer Council Victoria
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PU.1, C/EBPβ, leukemogenesis, myeloid leukemia, hematopoiesis, transcription factor expression, myeloid cells, lymphoid cells
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Hematopoiesis, Humans, Leukemia, Proto-Oncogene Proteins, Trans-Activators, Cell Lineage, CCAAT-Enhancer-Binding Protein-alpha
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