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Cited by 57Acute Myeloid Leukemia ResearchHematopoietic Stem Cell TransplantationCytokine Signaling Pathways and Interactions

Non‐steady‐state hematopoiesis regulated by the C/EBP β transcription factor

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Hirai, Hideyo, Yokota, Asumi, Tamura, Akihiro, Sato, Atsushi, Maekawa, Taira·2015·Cancer Science
DOI 10.1111/cas.12690PMC PMC4520629
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Abstract

Steady-state hematopoiesis responds to extracellular stimuli to meet changing demands and also to pathologically altered intracellular signaling. Granulocyte production increases following infection or in response to cytokine stimulation, and activation of the CCAAT/enhancer-binding protein β (C/EBPβ) transcription factor is required for such stress-induced granulopoiesis, whereas C/EBPα plays a critical role in maintaining steady-state granulopoiesis. Different roles of these C/EBP transcription factors in different modes of hematopoiesis are evolutionally conserved from zebrafish to humans. In addition to reactions against infections, C/EBPβ is responsible for cancer-driven myelopoiesis, which promotes cancer progression, at least in part, by abrogating the immune response in the cancer microenvironment. The BCR-ABL fusion protein activates emergency-specific pathway of granulopoiesis by upregulating C/EBPβ. This in turn causes chronic phase chronic myeloid leukemia, which is characterized by myeloid expansion. The C/EBPβ transcription factor also plays a role in other hematological malignancies of both myeloid and lymphoid lineage origin. Thus, elucidation of the upstream and downstream networks surrounding C/EBPβ will lead to the development of novel therapeutic strategies for diseases mediated by non-steady-state hematopoiesis.

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  • Mechanisms regulating emergency myelopoiesis are likely multifactorial, and transcriptional regulators such as C/EBPβ have also been implicated as drivers of hematopoietic responses to injury and infection.

    “The mechanisms regulating “emergency” myelopoiesis are likely multifactorial, and transcriptional regulators such as C/EBPβ have also been implicated as drivers of hematopoietic responses to injury and infection (Hirai et al., 2006; Hirai et al., 2015).”

    From PU.1 is required to restrain myelopoiesis during chronic inflammatory stress (2023) · cites this paper as Hirai et al., 2015

    The Emergency Granulopoiesis section says C/EBPβ is required for infection- or cytokine-induced granulocyte production. The Modes of Hematopoiesis section describes emergency responses to bleeding, but the passages do not establish C/EBPβ as a driver of responses specifically to injury. No page numbers were available in our copy. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Hirai, H., Yokota, A., Tamura, A., Sato, A., & Maekawa, T.
Affiliations
Kyoto University Hospital (JP)
Corresponding author
Hirai, Hideyo
ORCID
Venue
Cancer Science
Publisher
Wiley
Published
2015-06
Volume
106
Issue
7
Pages
797-802
ISSN
  • 1347-9032 (ISSN-L)
  • 1349-7006
DOI
10.1111/cas.12690
PMC
PMC4520629
OpenAlex
W2073306952
Cited by
57
References
3
Citations by year
2026: 8 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 1
FWCI
2.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Science (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by-nc)
Funders
  • grant from the Project for Development of Innovative Research on Cancer Therapeutics from MEXT in Japan
  • Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology
  • Grant-in-Aid from the Ministry of Health, Labor and Welfare in Japan
  • research grant from the Princess Takamatsu Cancer Research Fund
  • The National Cancer Center Research and Development Fund
  • the Takeda Science Foundation
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
C/EBPβ, C/EBPα, chronic myeloid leukemia, BCR-ABL, tumor microenvironment, hematologic malignancies, transcriptional regulation, myeloid expansion
MeSH terms
Congenital Bone Marrow Failure Syndromes, Animals, Hematopoiesis, Humans, Neutropenia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Gene Expression Regulation, Leukemic, CCAAT-Enhancer-Binding Protein-beta

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