Effects of C/EBPalpha and C/EBPbeta in BCR/ABL-Expressing Cells: Differences and Similarities

C/EBP alpha and C/EBP beta, two transcription factors of the C/EBP family play important roles in the proliferation and differentiation of various cell types including myeloid progenitors. Expression of C/EBP alpha and C/EBP beta is repressed in myeloid blast crisis of Chronic Myelogenous Leukemia by mechanisms that involve translation repression which depends on the interaction of RNA-binding proteins with conserved binding sites in the 5'UTR of c/ebp alpha and c/ebp beta mRNA. Ectopic expression of C/EBP alpha and C/EBP beta in myeloid progenitors expressing the BCR/ABL oncogene inhibits proliferation, induces differentiation and suppresses leukemogenesis in mice, but C/EBP a is markedly more effective than C/EBP beta. The more potent effects of C/EBP a probably depends on protein-protein interaction with cell-cycle regulatory proteins, but the pattern of genes modulated by C/EBP alpha and C/EBP beta is not completely overlapping. This suggests that transcription-dependent and -independent effects are both involved and support the therapeutic potential of reactivating C/EBP alpha and C/EBP beta expression in leukemic cells