Role of Transcription Factors C/EBPa and PU.1 in Normal Hematopoiesis and Leukemia
Abstract
Differentiation of hematopoietic stem and progenitor cells is under strict control of a regulatory network orchestrated by lineage-specific transcription factors. A block in normal differentiation is a major contributing factor in the development of solid tumors and leukemias. Cells from patients with acute myeloid leukemia (AML) frequently harbor mutated or dysregulated transcription factor genes, suggesting their involvement in leukemogenesis. As a consequence, these alterations diminish the pool of available molecules of a small number of critical transcription factors, such as CCAAT enhancer binding proteins, PU.1, GATA-1, and AML-1. In this review, we focus on the mechanisms of how this functional pool of transcription factors is maintained during normal and malignant hematopoiesis, including direct protein-protein interactions, competition for DNA binding, and the control of transcription factor genes by proximal and distal regulatory elements. Results of recent studies of mice carrying hypomorphic PU.1 alleles have indicated that reduction in the expression of a single transcription factor is capable of predisposing mice to AML. The implications of these findings for the study of hematopoiesis in the future as well as novel approaches to more disease-specific therapies are discussed.
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IL-1β-mediated repression of these genes may involve other transcriptional regulators aside from PU.1 including CEBPA.
“These data suggest IL-1β-mediated repression of these genes may involve other transcriptional regulators aside from PU.1 including CEBPA, which regulates many of the same genes (Koschmieder et al., 2005; Pundhir et al., 2018; Higa et al., 2021).”
From PU.1 is required to restrain myelopoiesis during chronic inflammatory stress (2023) · cites this paper as Koschmieder et al., 2005
Dysregulation of the PU.1 transcriptional network is a common phenotype associated with hematological malignancy, particularly diseases of the myeloid lineage.
“Dysregulation of the PU.1 transcriptional network is a common phenotype associated with hematological malignancy, particularly diseases of the myeloid lineage (Cook et al., 2004; Dakic et al., 2005; Koschmieder et al., 2005; Will et al., 2015; Sive et al., 2016; Aivalioti et al., 2022).”
From PU.1 is required to restrain myelopoiesis during chronic inflammatory stress (2023) · cites this paper as Koschmieder et al., 2005
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References 94 · Cited by 72
- Authors
- Koschmieder, S., Rosenbauer, F., Steidl, U., Owens, B. M., & Tenen, D. G.
- Affiliations
- Harvard University (US)
- Corresponding author
- Tenen, Daniel G.
- Venue
- International Journal of Hematology
- Published
- 2005-06-01
- Volume
- 81
- Issue
- 5
- Pages
- 368-377
- ISSN
- 0925-5710 (ISSN-L)
- OpenAlex
- W2018690972
- Cited by
- 72
- References
- 94
- Citations by year
- 2026: 2 · 2025: 4 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 5 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 3
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Hematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL056745, HL56745)
- National Cancer Institute (P01CA72009, P01CA072009)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- C/EBPα, PU.1, transcription factors, hematopoiesis, acute myeloid leukemia, leukemogenesis, hematopoietic stem and progenitor cells, lineage-specific transcription factors, GATA-1, protein-protein interaction, regulatory elements, leukemia predisposition
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Gene Expression Regulation, Hematopoiesis, Humans, Leukemia, Mutation, Proto-Oncogene Proteins, Transcription Factors, Trans-Activators, Cyclic AMP Response Element-Binding Protein, Mice, Activating Transcription Factor 2
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