Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia
(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:
https://lup.lub.lu.se/record/1618587
- author
- Reckzeh, Kristian LU and Cammenga, Jörg LU
- organization
- publishing date
- 2010
- 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
- Springer
- external identifiers
-
- wos:000277469000001
- pmid:20422469
- 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
- 2016-04-01 09:53:22
- date last changed
- 2022-06-22 06:19:54
@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}}, keywords = {{differentiation; Myeloid; C/EBP alpha; Transcription factor; AML; Leukemia; Bi-allelic mutation}}, language = {{eng}}, number = {{4}}, pages = {{557--568}}, publisher = {{Springer}}, 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}}, doi = {{10.1007/s12185-010-0573-1}}, volume = {{91}}, year = {{2010}}, }