Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

The CCAAT/enhancer binding protein alpha (C/EBPα or CEBPA) is the founding member of a family of related leucine zipper transcription factors that play important roles in myeloid differentiation. Targeted inactivation of C/EBPα in mice demonstrates its importance in the proper development and function of liver, adipose tissue, lung and haematopoietic tissues. C/EBPα is highly expressed in these differentiated tissues where it controls differentiation-dependent gene expression and inhibits cell proliferation. Learning more about the precise molecular functions of the C/EBPα protein and how these are affected by leukaemogenic mutations should lead to an improved understanding of the cellular functions that are disrupted in patients with AML. Decreased expression of C/EBPα but not C/EBPα mutation has been shown in patients with granulocytic leukaemias that are associated with translocations t(8;21), inv (16) or t(15;17). Derived fusion proteins repress C/EBPα expression. Differentiation therapy of some AML types is based on restoring C/EBPα function. However, apparently normal C/EBPα is overexpressed in BCP-ALL harbouring the translocation t(14; 19)(q32; q13). C/EBPα may exhibit oncogenic as well as tumour suppressor properties in human leukaemogenesis. C/EBPα mutations were not found in non-haematopoietic cancers. DNA hypermethylation of the upstream C/EBPα promoter region is responsible for very low C/EBPα expression in human lung and endometrial cancer. C/EBPα expression may be a biomarker for early detection of these cancers and DNA-modifying drugs such as demethylating agents and/or histone deacetylase inhibitors could be used in the treatment of these malignancies.

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