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C/EBP? deregulation results in differentiation arrest in acute myeloid leukemia.

ABSTRACT: C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBP? is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBP? hypermethylation/silencing. Similarly, C/EBP? was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBP?, as C/EBP? mediates C/EBP? suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation of Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced AML samples restored granulocytic differentiation. In addition, treatment of these leukemias with demethylating agents restored the C/EBP?-C/EBP? balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBP? mediates the myeloid differentiation arrest induced by C/EBP? deficiency and that targeting the C/EBP?-C/EBP? axis rescues neutrophilic differentiation in this unique subset of AMLs.

SUBMITTER: Alberich-Jorda M 

PROVIDER: S-EPMC3533560 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPγ is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, C/EBPγ was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPα, as C/EBPα mediates C/EBPγ suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Fu  ...[more]

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