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Cited by 26Acute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processesChromatin Remodeling and Cancer

Gain‐of‐Function Effects of N‐Terminal CEBPA Mutations in Acute Myeloid Leukemia

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Schmidt, Luisa, Heyes, Elizabeth, Grebien, Florian·2020·BioEssays
DOI 10.1002/bies.201900178PMC PMC7115832
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Abstract

Mutations in the CEBPA gene are present in 10–15% of acute myeloid leukemia (AML) patients. The most frequent type of mutations leads to the expression of an N‐terminally truncated variant of the transcription factor CCAAT/enhancer‐binding protein alpha (C/EBPα), termed p30. While initial reports proposed that p30 represents a dominant‐negative version of the wild‐type C/EBPα protein, other studies show that p30 retains the capacity to actively regulate gene expression. Recent global transcriptomic and epigenomic analyses have advanced the understanding of the distinct roles of the p30 isoform in leukemogenesis. This review outlines direct and indirect effects of the C/EBPα p30 variant on oncogenic transformation of hematopoietic progenitor cells and discusses how studies of N‐terminal CEBPA mutations in AML can be extrapolated to identify novel gain‐of‐function features in oncoproteins that arise from recurrent truncating mutations in transcription factors.

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  • Activated typical enhancers in HCC are associated with developmental GO terms and enriched for binding motifs of development-related TFs such as CEBPα/β, NK2-1, and ZIC3.

    “The activated typical enhancers were associated with developmental gene ontology (GO) terms and were enriched for binding motifs of development-related TFs such as CEBPα/β, NK2-1, and ZIC3 (Fig. 2a, b)55–57.”

    From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [56]

    The Introduction (page unavailable) identifies C/EBPα as a transcription factor necessary for the development of the liver and other tissues, supporting its description as development-related. The paper discusses C/EBPα binding motifs in leukemia, but does not report activated typical enhancers, developmental GO terms, or motif enrichment in HCC; it also does not substantiate the other named factors. (LLM, conf=0.86)

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Authors
Schmidt, L., Heyes, E., & Grebien, F.
Affiliations
University of Veterinary Medicine Vienna (AT)
Corresponding author
Grebien, Florian
ORCID
Venue
BioEssays
Publisher
Wiley
Published
2019-12-23
Volume
42
Issue
2
Pages
e1900178-e1900178
ISSN
  • 0265-9247 (ISSN-L)
  • 1521-1878
DOI
10.1002/bies.201900178
PMC
PMC7115832
OpenAlex
W2995560480
Cited by
26
References
61
Citations by year
2025: 6 · 2024: 7 · 2023: 7 · 2022: 2 · 2021: 3 · 2020: 1
FWCI
0.24
Type
journal article
Language
en
Open access
Licence
Locations
  • BioEssays (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
H2020 European Research Council (n° 636855/StG)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
CEBPA mutation, acute myeloid leukemia, gain-of-function mutations, hematopoietic progenitor cells, leukemogenesis, oncogenic transformation, dominant negative protein, gene expression regulation
MeSH terms
Gain of Function Mutation, Animals, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Acute, Gene Expression Regulation, Neoplastic, CCAAT-Enhancer-Binding Protein-alpha

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