| First Author | Alberich-Jordà M | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 12 | Pages | 4490-504 |
| PubMed ID | 23160200 | Mgi Jnum | J:193970 |
| Mgi Id | MGI:5469995 | Doi | 10.1172/JCI65102 |
| Citation | Alberich-Jorda M, et al. (2012) C/EBPgamma deregulation results in differentiation arrest in acute myeloid leukemia. J Clin Invest 122(12):4490-504 |
| abstractText | C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPgamma is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPalpha hypermethylation/silencing. Similarly, C/EBPgamma was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPalpha, as C/EBPalpha mediates C/EBPgamma 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/EBPalpha-C/EBPgamma balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPgamma mediates the myeloid differentiation arrest induced by C/EBPalpha deficiency and that targeting the C/EBPalpha-C/EBPgamma axis rescues neutrophilic differentiation in this unique subset of AMLs. |
