Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation.
One of the most studied transcription
factors in hematopoiesis is the leucine
zipper CCAAT-enhancer binding proteina
(C/EBPα), which is mainly involved in cell
fate decisions for myeloid differentiation.
Its involvement in acute myeloid leukemia
(AML) is diverse, with patients frequently
exhibiting mutations, deregulation of gene
expression, or alterations in the function of
C/EBPα. In this review, we emphasize the
importance of C/EBPα for neutrophil maturation,
its role in myeloid priming of hematopoietic
stem and progenitor cells, and its
indispensable requirement for AML development.
We discuss that mutations in the open reading frame of CEBPA lead to an altered C/EBPa function, affecting the expression of downstream genes and consequently deregulating myelopoiesis. The emerging transcriptional mechanisms of CEBPA are discussed based on recent studies. Novel insights on howthese mechanisms may be deregulated by oncoproteins or mutations/variants in CEBPA enhancers are suggested in principal to reveal novel mechanisms of how CEBPA is deregulated at the transcriptional level.
|Sponsor||This work was supported by the Dutch Cancer Foundation “Konining Wilhelmina Fonds” and the Ladt Tata Memorial Trust Foundation.|
|Persistent URL||dx.doi.org/10.1182/blood-2016-09- 687822, hdl.handle.net/1765/106478|
Avellino, R, & Delwel, H.R. (2017). Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation. Blood, 129(15), 2083–2091. doi:10.1182/blood-2016-09- 687822