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 protein α (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 ofCEBPAlead to an altered C/EBPα function, affecting the expression of downstream genes and consequently deregulating myelopoiesis. The emerging transcriptional mechanisms ofCEBPAare discussed based on recent studies. Novel insights on how these mechanisms may be deregulated by oncoproteins or mutations/variants inCEBPAenhancers are suggested in principal to reveal novel mechanisms of howCEBPAis deregulated at the transcriptional level.
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Roberto
R
Avellino
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Ruud
R
Delwel
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D038042:Myelopoiesis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D016366:Open Reading Frames
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D009363:Neoplasm Proteins