Please use this identifier to cite or link to this item: https://doi.org/10.1172/JCI65102
Title: C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
Authors: Alberich-Jordà, M.
Wouters, B.
Balastik, M.
Shapiro-Koss, C.
Zhang, H.
DiRuscio, A.
Radomska, H.S.
Ebralidze, A.K.
Amabile, G.
Ye, M.
Zhang, J.
Lowers, I.
Avellino, R.
Melnick, A.
Figueroa, M.E.
Valk, P.J.M.
Delwel, R.
Tenen, D.G. 
Issue Date: 3-Dec-2012
Citation: Alberich-Jordà, M., Wouters, B., Balastik, M., Shapiro-Koss, C., Zhang, H., DiRuscio, A., Radomska, H.S., Ebralidze, A.K., Amabile, G., Ye, M., Zhang, J., Lowers, I., Avellino, R., Melnick, A., Figueroa, M.E., Valk, P.J.M., Delwel, R., Tenen, D.G. (2012-12-03). C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia. Journal of Clinical Investigation 122 (12) : 4490-4504. ScholarBank@NUS Repository. 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.
Source Title: Journal of Clinical Investigation
URI: http://scholarbank.nus.edu.sg/handle/10635/125365
ISSN: 00219738
DOI: 10.1172/JCI65102
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

34
checked on Oct 15, 2019

WEB OF SCIENCETM
Citations

33
checked on Oct 15, 2019

Page view(s)

43
checked on Oct 11, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.