International Journal of Hematology

, Volume 91, Issue 4, pp 557–568

Molecular mechanisms underlying deregulation of C/EBPα in acute myeloid leukemia

Review Article


The CEBPA gene encodes a transcription factor protein that is crucial for granulocytic differentiation, regulation of myeloid gene expression and growth arrest. Mutations in one or both alleles of CEBPA are observed in about 10% of patients with acute myeloid leukemia (AML). Moreover, other genetic events associated with AML have been identified to deregulate C/EBPα expression and function at various levels. Recently developed mouse models that accurately mimic the genetic C/EBPα alterations in human AML demonstrate C/EBPα’s gatekeeper function in the control of self-renewal and lineage commitment of hematopoietic stem cells (HSCs). Moreover, these studies indicate that CEBPA mutations affect HSCs in early leukemia development by inducing proliferation and limiting their lineage potential. However, the exact relationship between ‘pre-leukemic’ HCSs and those cells that finally initiate leukemia (leukemia-initiating cells) with disturbed differentiation and aberrant proliferation remains elusive. More research is needed to identify and characterize these functionally distinct populations and the exact role of the different genetic alterations in the process of leukemia initiation and maintenance.


AML Leukemia Transcription factor C/EBPα Myeloid differentiation Bi-allelic mutation 


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Copyright information

© The Japanese Society of Hematology 2010

Authors and Affiliations

  1. 1.Department of Molecular Medicine and Gene Therapy, Lund Stem Cell CenterLund UniversityLundSweden
  2. 2.Department of HematologyLund UniversityLundSweden

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