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Cited by 94Acute Myeloid Leukemia ResearchHematopoietic Stem Cell TransplantationGenomics and Chromatin Dynamics

The RUNX1–PU.1 axis in the control of hematopoiesis

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Imperato, Maria Rosaria, Cauchy, Pierre, Obier, Nadine, Bonifer, Constanze·2015·International Journal of Hematology
DOI 10.1007/s12185-015-1762-8
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Abstract

The differentiation from multipotent hematopoietic stem cells (HSC) to mature and functional blood cells requires the finely tuned regulation of gene expression at each stage of development. Specific transcription factors play a key role in this process as they modulate the expression of their target genes in an exquisitely lineage-specific manner. A large number of important transcriptional regulators have been identified which establish and maintain specific gene expression patterns during hematopoietic development. Hematopoiesis is therefore a paradigm for investigating how transcription factors function in mammalian cells, thanks also to the evolution of genome-wide and the next-generation sequencing technologies. In this review, we focus on the current knowledge of the biological and functional properties of the hematopoietic master regulator RUNX1 (also known as AML1, CBFA2, PEBP2aB) transcription factor and its main downstream target PU.1. We will outline their relationship in determining the fate of the myeloid lineage during normal stem cell development and under conditions when hematopoietic development is subverted by leukemic transformation.

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  • PU.1 action is important or indispensable for sustained generation of all known hematopoietic precursors with lymphoid developmental potentials.

    “its action is also important or indispensable for sustained generation of all known hematopoietic precursors that have lymphoid developmental potentials (1–9).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [9]

    The sections “Developmental-stage-specific RUNX1 and PU.1 function” and “RUNX1 and PU.1 in T and B-cells” (page numbers unavailable) describe PU.1’s contribution to HSC maintenance and its importance in early T-cell development and B-cell progenitor formation. They do not establish that PU.1 is important or indispensable for the sustained generation of *all known* hematopoietic precursors with lymphoid potential. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • In pro-T cells, a key positive regulatory partner of PU.1 is Runx1, which has long been known to interact with PU.1 to form a functional complex at myeloid positive regulatory target sites.

    “For PU.1 in pro-T cells, IRF and C/EBP family partners are mostly not available, but a key positive regulatory partner is Runx1 (previously known as AML1 or CBFα2), which has long been known to interact with PU.1 (and C/EBPα) to form a functional complex at its myeloid positive regulatory target sites (9, 112, 113).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [9]

    The ‘Developmental-stage-specific RUNX1 and PU.1 function’ section says RUNX1 and PU.1 form a synergistic complex in myeloid cells that regulates lineage-specific genes. The ‘RUNX1 and PU.1 in T and B-cells’ section discusses each factor’s role in early T-cell development but does not establish that RUNX1 is a key positive partner of PU.1 in pro-T cells. Page numbers are unavailable in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Authors
Imperato, M. R., Cauchy, P., Obier, N., & Bonifer, C.
Affiliations
University of Birmingham (GB)
Corresponding author
Bonifer, Constanze
ORCID
Venue
International Journal of Hematology
Publisher
Springer Science and Business Media LLC
Published
2015-03-08
Volume
101
Issue
4
Pages
319-329
ISSN
  • 0925-5710 (ISSN-L)
  • 1865-3774
DOI
10.1007/s12185-015-1762-8
OpenAlex
W2062896748
Cited by
94
References
137
Citations by year
2026: 5 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 3 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 9 · 2017: 9 · 2016: 8 · 2015: 4
FWCI
1.50
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • International Journal of Hematology (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders
  • Leukaemia and Lymphoma Research
  • Directorate for Biological Sciences
  • Medical Research Council (MR/M009157/1)
  • Biotechnology and Biological Sciences Research Council (BB/I001220/2)
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
RUNX1, PU.1, hematopoiesis, hematopoietic stem cells, transcription factors, myeloid lineage, lineage specification, gene expression regulation, leukemic transformation
MeSH terms
Proto-Oncogene Protein Spi-1, Animals, B-Lymphocytes, Hematopoiesis, Humans, Proto-Oncogene Proteins, T-Lymphocytes, Signal Transduction, Leukemia, Myeloid, Acute, Transcriptional Activation, Trans-Activators, Gene Expression Regulation, Leukemic, Epigenesis, Genetic, Core Binding Factor Alpha 2 Subunit

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