title: Regulation of the C/EBPα signaling pathway in acute myeloid leukemia (Review).
abstract: The transcription factor CCAAT/enhancer binding protein α (C/EBPα), as a critical regulator of myeloid development, directs granulocyte and monocyte differentiation. Various mechanisms have been identified to explain how C/EBPα functions in patients with acute myeloid leukemia (AML). C/EBPα expression is suppressed as a result of common leukemia-associated genetic and epigenetic alterations such as AML1-ETO, RARα-PLZF or gene promoter methylation. Recent data have shown that ubiquitination modification also contributes to its downregulation. In addition, 10-15% of patients with AML in an intermediate cytogenetic risk subgroup were characterized by mutations of the C/EBPα gene. As a transcription factor, C/EBPα can translocate into the nucleus and further regulate a variety of genes directly or indirectly, which are all key factors for cell differentiation. This review summarizes recent reports concerning the dysregulation of C/EBPα expression at various levels in human AML. The currently available data are persuasive evidence suggesting that impaired abnormal C/EBPα expression contributes to the development of AML, and restoration of C/EBPα expression as well as its function represents a promising target for novel therapeutic strategies in AML.
authors.affiliation: Department of Hemato-Oncology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare and Uncommon Diseases, Key Medical Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology of Shandong Province, Jinan, Shandong 250062, P.R. China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Song
authors.affiliation: Research Center for Medical Biotechnology, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, Qianfoshan Mountain Hospital of Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Kehong
authors.initials: K
authors.lastname: Bi
authors.affiliation: Department of Hemato-Oncology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare and Uncommon Diseases, Key Medical Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology of Shandong Province, Jinan, Shandong 250062, P.R. China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Jiang
mesh_terms: D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha