Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation

被引：133

作者：

Avellino, Roberto ^{[1
]}

Delwel, Ruud ^{[1
]}

机构：

[1] Erasmus MC, Dept Hematol, Doctor Molewaterplein 50,3015, Rotterdam, Netherlands

来源：

BLOOD | 2017年 / 129卷 / 15期

关键词：

ACUTE MYELOID-LEUKEMIA; BINDING-PROTEIN-ALPHA; BIALLELIC CEBPA MUTATIONS; C-JUN EXPRESSION; GENE-EXPRESSION; STEM-CELLS; GRANULOCYTIC DIFFERENTIATION; TRANSCRIPTIONAL CONTROL; CHROMATIN ARCHITECTURE; UNIPARENTAL DISOMY;

D O I：

10.1182/blood-2016-09-687822

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

One of the most studied transcription factors in hematopoiesis is the leucine zipper CCAAT-enhancer binding proteina (C/EBP alpha), 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/EBP alpha. In this review, we emphasize the importance of C/EBP alpha 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/EBP alpha 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.

引用

页码：2083 / 2091

页数：9

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