C/EBPα deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo

Transcriptional dysregulation during myeloid transformation in AML

“…Given the role of CEBPA for normal neutrophil development, this may be surprising. However, several recent reports have established the importance of CEBPA for monocytic differentiation (Liu et al, 2003;Heath et al, 2004. The gene expression studies in AML patients contrast with in vitro data indicating that CEBPA mRNA is repressed by FLT3/ITD signaling in 32D cells (Bullinger et al, 2004;Valk et al, 2004;Zheng et al, 2004).…”

Mutation of C/EBPα predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen

“…Cebpa-null fetal livers (Cebpa-null mice suffer from perinatal lethality) lack granulocytic cells and are arrested at the transition between the common myeloid progenitor (CMP) and the granulocyte macrophage progenitor (GMP). [5][6][7] Similar observations in an Mx1-Cre-driven conditional knockout of C/EBP␣ in adult mice suggest that C/EBP␣ plays similar roles in fetal and adult hematopoiesis. 6 Finally, C/EBP␣ has been proposed to act as an inhibitor of erythroid differentiation.…”

Molecular and cellular effects of oncogene cooperation in a genetically accurate AML mouse model

“…Affirmatively, in the absence of C/EBPa, no AML was observed in a transgenic mouse model, probably because of the requirement of C/EBPa for myeloid lineage commitment in the pathogenesis of AML. 8,9 The molecular mechanisms behind CEBPA mutations in AML development are not entirely clear. The spectrum of CEBPA mutations observed in AML includes N-terminal mutations blocking the translation of the 42 kDa isoform (p42) while allowing the 30 kDa isoform (p30) to be expressed, and C-terminal mutations generating in-frame insertions/deletions within the basic region leucine zipper DNA binding domain disrupting dimerization and DNA binding of both isoforms.…”