Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia

Research output: Contribution to journalReview article

Abstract

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/EBP alpha expression and function at various levels. Recently developed mouse models that accurately mimic the genetic C/EBP alpha alterations in human AML demonstrate C/EBP alpha'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.

Details

Authors
  • Kristian Reckzeh
  • Jörg Cammenga
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • differentiation, Myeloid, C/EBP alpha, Transcription factor, AML, Leukemia, Bi-allelic mutation
Original languageEnglish
Pages (from-to)557-568
JournalInternational Journal of Hematology
Volume91
Issue number4
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes