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Ref Type Journal Article
PMID (26601784)
Authors Ohlsson E, Schuster MB, Hasemann M, Porse BT
Title The multifaceted functions of C/EBPα in normal and malignant haematopoiesis.
Journal Leukemia
Vol 30
Issue 4
Date 2016 Apr
URL
Abstract Text The process of blood formation, haematopoiesis, depends upon a small number of haematopoietic stem cells (HSCs) that reside in the bone marrow. Differentiation of HSCs is characterised by decreased expression of genes associated with self-renewal accompanied by a stepwise activation of genes promoting differentiation. Lineage branching is further directed by groups of cooperating and counteracting genes forming complex networks of lineage-specific transcription factors. Imbalances in such networks can result in blockage of differentiation, lineage reprogramming and malignant transformation. CCAAT/enhancer-binding protein-α (C/EBPα) was originally identified 30 years ago as a transcription factor that binds both promoter and enhancer regions. Most of the early work focused on the role of C/EBPα in regulating transcriptional processes as well as on its functions in key differentiation processes during liver, adipogenic and haematopoietic development. Specifically, C/EBPα was shown to control differentiation by its ability to coordinate transcriptional output with cell cycle progression. Later, its role as an important tumour suppressor, mainly in acute myeloid leukaemia (AML), was recognised and has been the focus of intense studies by a number of investigators. More recent work has revisited the role of C/EBPα in normal haematopoiesis, especially its function in HSCs, and also started to provide more mechanistic insights into its role in normal and malignant haematopoiesis. In particular, the differential actions of C/EBPα isoforms, as well as its importance in chromatin remodelling and cellular reprogramming, are beginning to be elucidated. Finally, recent work has also shed light on the dichotomous function of C/EBPα in AML by demonstrating its ability to act as both a tumour suppressor and promoter. In the present review, we will summarise the current knowledge on the functions of C/EBPα during normal and malignant haematopoiesis with special emphasis on the recent work.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
CEBPA NCBI C/EBP-alpha|CEBP CEBPA, CCAAT enhancer binding protein alpha, is a transcription factor that regulates the expression of genes involved in cell differentiation (PMID: 26601784). Inactivation of CEBPA is associated with the pathogenesis of leukemia, including biallelic CEBPA-mutant AML (PMID: 32086816), and dysregulation of CEBPA has been identified in various solid tumors (PMID: 28720765, PMID: 28504718). Tumor suppressor
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CEBPA mutant acute myeloid leukemia not applicable N/A Clinical Study Prognostic In clinical analyses, biallelic CEBPA mutations were associated with favorable clinical outcome in patients with cytogenetically normal acute myeloid leukemia (PMID: 26601784, PMID: 19171880, PMID: 20038735, PMID: 22915647). 22915647 26601784 19171880 20038735