Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 1 May 2007, Vol. 109, No. 9, pp. 3895-3905.
Prepublished online as a Blood First Edition Paper on January 18, 2007; DOI 10.1182/blood-2006-08-040147.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Tables and Figure
Right arrow All Versions of this Article:
blood-2006-08-040147v1
109/9/3895    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Agrawal, S.
Right arrow Articles by Müller-Tidow, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Agrawal, S.
Right arrow Articles by Müller-Tidow, C.
Related Collections
Right arrow Neoplasia
Right arrow Oncogenes and Tumor Suppressors
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

NEOPLASIA

The C/EBP{delta} tumor suppressor is silenced by hypermethylation in acute myeloid leukemia

Shuchi Agrawal1, Wolf-Karsten Hofmann2, Nicola Tidow1, Mathias Ehrich3, Dirk van den Boom3, Steffen Koschmieder1, Wolfgang E. Berdel1, Hubert Serve1, and Carsten Müller-Tidow1

1 Department of Medicine, Hematology and Oncology, University of Münster, Germany; 2 Department of Oncology and Hematology, University Hospital Benjamin Franklin, Berlin, Germany; 3 Sequenom, San Diego, CA

Aberrant DNA methylation is the most frequent molecular alteration in acute myeloid leukemia (AML). To identify methylation-silenced genes in AML, we performed microarray analyses in U937 cells exposed to the demethylating agent 5-aza-deoxy-cytidine. Overall, 274 transcripts were significantly induced. Interestingly, C/EBP{delta} expression was significantly induced (more than 10-fold) by demethylation whereas expression of all other C/EBP family members remained unchanged. The C/EBP{delta} promoter was strongly methylated in different leukemic cell lines and showed signs of a repressed chromatin state. Analyses of the promoter regions of the entire C/EBP family ({alpha}, ß, {gamma}, {delta}, {epsilon}, {zeta}) in bone marrow samples from AML patients (n = 80) and controls (n = 15) by mass spectrometry revealed that C/EBP{delta} is the most commonly hypermethylated C/EBP gene in AML. Hypermethylation occurred in more than 35% of AML patients at primary diagnosis. A significant correlation (P = .016) was observed between hypermethylation of the C/EBP{delta} promoter and low expression of C/EBP{delta} in AML patients. C/EBP{delta} promoter activity was strongly repressed by methylation in vitro, and transcriptional repression partially depended on MeCP2 activity. C/EBP{delta} exhibited growth-inhibitory properties in primary progenitor cells as well as in Flt3-ITD–transformed cells. Taken together, C/EBP{delta} is a novel tumor suppressor gene in AML that is silenced by promoter methylation.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
C.-Y. Ko, H.-C. Hsu, M.-R. Shen, W.-C. Chang, and J.-M. Wang
Epigenetic Silencing of CCAAT/Enhancer-binding Protein {delta} Activity by YY1/Polycomb Group/DNA Methyltransferase Complex
J. Biol. Chem., November 7, 2008; 283(45): 30919 - 30932.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
H. Kroeger, J. Jelinek, M. R. H. Estecio, R. He, K. Kondo, W. Chung, L. Zhang, L. Shen, H. M. Kantarjian, C. E. Bueso-Ramos, et al.
Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse
Blood, August 15, 2008; 112(4): 1366 - 1373.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Zhou, J. Si, T. Liu, and J. W. DeWille
PIASy Represses CCAAT/Enhancer-binding Protein {delta} (C/EBP{delta}) Transcriptional Activity by Sequestering C/EBP{delta} to the Nuclear Periphery
J. Biol. Chem., July 18, 2008; 283(29): 20137 - 20148.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Muller-Tidow and S. Koschmieder
The hidden faces of C/EBP{beta}
Blood, March 15, 2008; 111(6): 2949 - 2950.
[Full Text] [PDF]

Home page
 BloodHome page
B. J. Wouters, M. A. Jorda, K. Keeshan, I. Louwers, C. A. J. Erpelinck-Verschueren, D. Tielemans, A. W. Langerak, Y. He, Y. Yashiro-Ohtani, P. Zhang, et al.
Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1
Blood, November 15, 2007; 110(10): 3706 - 3714.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020