Growth-inhibiting Activity of Transcription Factor C/EBPα, Its Role in Haematopoiesis and Its Tumour Suppressor or Oncogenic Properties in Leukaemias (C/EBPα / cell cycle / proliferation / differentiation / haematopoiesis / leukaemia / tumour suppressor)

The CCAAT/enhancer binding protein alpha (C/EBPα or CEBPA) is the founding member of a fam- ily of related leucine zipper transcription factors that play important roles in myeloid differentiation. Target- ed inactivation of C/EBPα in mice demonstrates its im- portance in the proper development and function of liver, adipose tissue, lung and haematopoietic tissues. C/EBPα is highly expressed in these differentiated tis- sues 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 leu- kaemogenic mutations should lead to an improved un- derstanding 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 fu- sion proteins repress C/EBPα expression. Differentia- tion therapy of some AML types is based on restoring C/EBPα function. However, apparently normal C/EBPα