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C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
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SYSNO ASEP 0387490 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia Author(s) Alberich-Jorda, M. (US)
Wouters, B. (NL)
Balaštík, Martin (UMG-J)
Shapiro-Koss, C. (NL)
Zhang, H. (US)
DiRuscio, A. (US)
Radomska, H.S. (US)
Ebralidze, A.K. (US)
Amabile, G. (US)
Ye, M. (US)
Zhang, J.Y. (US)
Lowers, I. (NL)
Avellino, R. (NL)
Melcnick, A. (US)
Figueroa, M.E. (US)
Valk, P.J.M. (NL)
Delwel, R. (NL)
Tenen, D.G. (US)Source Title Journal of Clinical Investigation. - : American Society for Clinical Investigation - ISSN 0021-9738
Roč. 122, č. 12 (2012), s. 4490-4504Number of pages 15 s. Language eng - English Country US - United States Keywords C/EBP transcription factor ; acute myeloid leukemia ; differentiation Subject RIV EB - Genetics ; Molecular Biology Institutional support UMG-J - RVO:68378050 UT WOS 000311926200024 DOI 10.1172/JCI65102 Annotation 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. 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/EBPα-C/EBPγ balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPγ mediates the myeloid differentiation arrest induced by C/EBPα deficiency and that targeting the C/EBPα-C/EBPγ axis rescues neutrophilic differentiation in this unique subset of AMLs. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2013
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