标题：Regulation of the C/EBP alpha signaling pathway in acute myeloid leukemia (Review)
作者：Song, Guanhua;Wang, Lin;Bi, Kehong;Jiang, Guosheng
作者机构：[Song, G] Department of Hemato-Oncology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, 18877 Jingshi Road, Jinan, Shandong, 25006 更多
通讯作者地址：[Bi, K]Shandong Univ, Qianfoshan Mt Hosp, Dept Hematol, Jingshi Rd, Jinan 250014, Shandong, Peoples R China.
摘要：The transcription factor CCAAT/enhancer binding protein a (C/EBP alpha), as a critical regulator of myeloid development, directs granulocyte and monocyte differentiation. Various mechanisms have been identified to explain how C/EBP alpha functions in patients with acute myeloid leukemia (AML). C/EBP alpha expression is suppressed as a result of common leukemia-associated genetic and epigenetic alterations such as AML1-ETO, RAR alpha-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/EBP alpha gene. As a transcription factor, C/EBP alpha 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/EBP alpha expression at various levels in human AML. The currently available data are persuasive evidence suggesting that impaired abnormal C/EBP alpha expression contributes to the development of AML, and restoration of C/EBP alpha expression as well as its function represents a promising target for novel therapeutic strategies in AML.