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 2015 (6)
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|---|---|---|
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Pharmacological inhibition of fatty acid oxidation synergistically enhances the effect of L-asparaginase in childhood ALL cells
I Heřmanová, A Arruabarrena-Aristorena, K Vališ, H Nůsková, MA Jorda, K Fišer, S Fernández-Ruiz, D Kavan, A Pecinová, M Niso-Santano, M Žaliová, P Novák, J Houštěk, T Mráček, G Kroemer, A Carracedo, J Trka, J Starková |
Leukemia | 2015 |
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C/EBPα in normal and malignant myelopoiesis
AD Friedman |
International Journal of Hematology | 2015 |
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The +37 kb Cebpa Enhancer Is Critical for Cebpa Myeloid Gene Expression and Contains Functional Sites that Bind SCL, GATA2, C/EBPα, PU.1, and Additional Ets Factors
S Cooper, H Guo, AD Friedman, T Langmann |
PloS one | 2015 |
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CEBPA methylation and mutation in myelodysplastic syndrome
X Wen, J Hu, J Yang, W Qian, D Yao, Z Deng, Y Zhang, X Zhu, H Guo, J Lin, J Qian |
Medical Oncology | 2015 |
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C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4
CJ Huggins, MK Mayekar, N Martin, KL Saylor, M Gonit, P Jailwala, M Kasoji, DC Haines, OA Quiñones, PF Johnson |
Molecular and cellular biology | 2015 |
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The multifaceted functions of C/EBPα in normal and malignant haematopoiesis
E Ohlsson, MB Schuster, M Hasemann, BT Porse |
Leukemia | 2015 |
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