Advanced

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

Reckzeh, Kristian LU and Cammenga, Jörg LU (2010) In International Journal of Hematology 91(4). p.557-568
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
differentiation, Myeloid, C/EBP alpha, Transcription factor, AML, Leukemia, Bi-allelic mutation
in
International Journal of Hematology
volume
91
issue
4
pages
557 - 568
publisher
Carden Jennings Publishing Co., Ltd.
external identifiers
  • wos:000277469000001
  • pmid:20422469
  • scopus:85027927682
ISSN
0925-5710
DOI
10.1007/s12185-010-0573-1
language
English
LU publication?
yes
id
5ed0ab97-ecba-4817-b8aa-0017e5ad1643 (old id 1618587)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20422469?dopt=Abstract
date added to LUP
2010-06-18 15:43:33
date last changed
2018-06-10 03:02:48
@article{5ed0ab97-ecba-4817-b8aa-0017e5ad1643,
  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.},
  author       = {Reckzeh, Kristian and Cammenga, Jörg},
  issn         = {0925-5710},
  keyword      = {differentiation,Myeloid,C/EBP alpha,Transcription factor,AML,Leukemia,Bi-allelic mutation},
  language     = {eng},
  number       = {4},
  pages        = {557--568},
  publisher    = {Carden Jennings Publishing Co., Ltd.},
  series       = {International Journal of Hematology},
  title        = {Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia},
  url          = {http://dx.doi.org/10.1007/s12185-010-0573-1},
  volume       = {91},
  year         = {2010},
}