Gain-of-Function Effects of N-Terminal CEBPA Mutations in Acute Myeloid Leukemia.
Luisa SchmidtElizabeth HeyesFlorian GrebienPublished in: BioEssays : news and reviews in molecular, cellular and developmental biology (2019)
Mutations in the CEBPA gene are present in 10-15% of acute myeloid leukemia (AML) patients. The most frequent type of mutations leads to the expression of an N-terminally truncated variant of the transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα), termed p30. While initial reports proposed that p30 represents a dominant-negative version of the wild-type C/EBPα protein, other studies show that p30 retains the capacity to actively regulate gene expression. Recent global transcriptomic and epigenomic analyses have advanced the understanding of the distinct roles of the p30 isoform in leukemogenesis. This review outlines direct and indirect effects of the C/EBPα p30 variant on oncogenic transformation of hematopoietic progenitor cells and discusses how studies of N-terminal CEBPA mutations in AML can be extrapolated to identify novel gain-of-function features in oncoproteins that arise from recurrent truncating mutations in transcription factors.
Keyphrases
- transcription factor
- acute myeloid leukemia
- binding protein
- gene expression
- end stage renal disease
- wild type
- allogeneic hematopoietic stem cell transplantation
- ejection fraction
- poor prognosis
- dna methylation
- chronic kidney disease
- dna binding
- genome wide identification
- prognostic factors
- bone marrow
- genome wide
- peritoneal dialysis
- patient reported outcomes
- amino acid
- patient reported