Citations to this article
Citation Information: J Clin Invest. 2012;122(12):4490-4504. https://doi.org/10.1172/JCI65102.
Abstract
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.
Authors
Meritxell Alberich-Jordà, Bas Wouters, Martin Balastik, Clara Shapiro-Koss, Hong Zhang, Annalisa DiRuscio, Hanna S. Radomska, Alexander K. Ebralidze, Giovanni Amabile, Min Ye, Junyan Zhang, Irene Lowers, Roberto Avellino, Ari Melnick, Maria E. Figueroa, Peter J.M. Valk, Ruud Delwel, Daniel G. Tenen
Total citations by year
Citations to this article in year 2017 (5)
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AA Wurm, P Zjablovskaja, M Kardosova, D Gerloff, D Bräuer-Hartmann, C Katzerke, JU Hartmann, T Benoukraf, S Fricke, N Hilger, AM Müller, M Bill, S Schwind, DG Tenen, D Niederwieser, M Alberich-Jorda, G Behre |
Nature Communications | 2017 |
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EVI2B is a C/EBPα target gene required for granulocytic differentiation and functionality of hematopoietic progenitors
P Zjablovskaja, M Kardosova, P Danek, P Angelisova, T Benoukraf, AA Wurm, T Kalina, S Sian, M Balastik, R Delwel, T Brdicka, DG Tenen, G Behre, F Fiore, B Malissen, V Horejsi, M Alberich-Jorda |
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Nature Communications | 2017 |
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A Morel, A Baguet, J Perrard, C Demeret, E Jacquin, D Guenat, C Mougin, JL Prétet |
Oncotarget | 2017 |
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ZNF143 protein is an important regulator of the myeloid transcription factor C/EBPα
D Gonzalez, A Luyten, B Bartholdy, Q Zhou, M Kardosova, A Ebralidze, KD Swanson, HS Radomska, P Zhang, SS Kobayashi, RS Welner, E Levantini, U Steidl, G Chong, S Collombet, MH Choi, AD Friedman, LM Scott, M Alberich-Jorda, DG Tenen |
The Journal of biological chemistry | 2017 |
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