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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v16.i1-2.90
pages 93-102

C/EBPα Dysregulation in AML and ALL

Ido Paz-Priel
Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Alan Friedman
Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland


The transcription factor CCAAT/enhancer binding protein a (C/EBPα) is a critical regulator of myeloid development, directing granulocyte, and monocyte differentiation. As such, it is dysregulated in more than half of patients with acute myeloid leukemia (AML). C/EBPα expression is suppressed as result of common leukemia-associated genetic and epigenetic alterations such as AML1-ETO, BCR-ABL, FLT3-ITD, or CEBPA promoter methylation. In addition, 10-15% of patients with AML with intermediate risk cytogenetics are characterized by mutations of the CEBPA gene. Two classes of mutations are described. N-terminal changes result in expression of a truncated dominant negative C/EBPαp30 isoform. C-terminal mutations are in-frame insertions or deletions resulting in alteration of the leucine zipper preventing dimerization and DNA binding. Often, patients carry both N- and C-terminal mutations each affecting a different allele, and a mouse model recapitulates the human phenotype. Patients with mutated CEBPA AML comprise a clinically distinct group with favorable outcome consistently seen in patients with biallelic mutations. In addition, C/EBP family members are aberrantly expressing from the immunoglobulin heavy chain locus in 2% of pre-B ALLs. This review summarizes the normal hematopoietic developmental pathways regulated by C/EBPα and discusses the molecular pathways involved in mutated CEBPA AML and ALL.

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