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C/EBPα mutations in acute myeloid leukaemias

Nature Reviews Cancer volume 4, pages 394–400 (2004)Cite this article

Key Points

  • CCAAT/enhancer-binding protein-α (C/EBPα) is a transcription factor that coordinates cellular differentiation with growth arrest.

  • Patients with acute myeloid leukaemia carry specific combinations of point mutations in the gene encoding C/EBPα.

  • C/EBPα represses the E2F transcription factor. Patient-derived C/EBPα mutants generally loose the ability to bind DNA or to repress E2F activity.

  • C/EBPα expression inhibits the malignant potential of myeloid leukaemia cells by inducing their differentiation.

  • E2F repression and DNA binding by C/EBPα are required for the C/EBP-induced differentiation of leukaemia cells.

  • Reconstituting C/EBPα-mediated E2F repression has the potential to revert leukaemogenesis in vivo.

Abstract

Specific mutations in the gene that encodes the multifunctional transcription factor C/EBPα are frequently associated with acute myeloid leukaemias. Are only a specific subset of the functions of C/EBPα therefore involved in leukaemogenesis?

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Figure 1: Regulation of the C/EBPα p42/p30 ratio.
Figure 2: Distribution of C/EBPα mutations in acute myeloid leukaemia cells.
Figure 3: Distribution of C/EBPα functions.
Figure 4: Mutant forms of C/EBPα and acute myeloid leukaemia.

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Acknowledgements

The author thanks B. Porse, A. Leutz and D. Tenen for helpful discussions, and present as well as former members of the Nerlov lab for their contributions to this article.

Correction: The DOI number given for this article in the May 2004 print issue of Nature Reviews Cancer was wrong. The correct DOI number is: doi:10.1038/nrc1363.

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Authors and Affiliations

  1. Mouse Biology Programme, European Molecular Biology Laboratory, via Ramarini 32, Monterotondo, 00016, Italy

    Claus Nerlov

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  1. Claus Nerlov
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DATABASES

Cancer.gov

acute myeloid leukaemia

LocusLink

C/EBPα

C/EBPβ

C/EBPε

CBFβ

CBP

c-MYC

eIF2α

eIF4E

ETS1

GATA1

p300

PU.1

RB

RUNX1

TBP

TFIIB

Glossary

BASELINE GRANULOPOIESIS

Normal physiological granulopoiesis, in which a myeloblast matures into a fully differentiated granulocyte, typically takes about 11–12 days. This is opposed to the accelerated granulopoiesis that occurs under conditions of stress, such as in the case of severe infection, when granulocytes are produced much more rapidly.

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Nerlov, C. C/EBPα mutations in acute myeloid leukaemias. Nat Rev Cancer 4, 394–400 (2004). https://doi.org/10.1038/nrc1363

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