Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2010
Språk
Engelska
Sidor
557-568
Publikation/Tidskrift/Serie
International Journal of Hematology
Volym
91
Issue
4
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Springer
Ämne
- Cell and Molecular Biology
Nyckelord
- differentiation
- Myeloid
- C/EBP alpha
- Transcription factor
- AML
- Leukemia
- Bi-allelic mutation
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0925-5710