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 First Edition Paper, prepublished online November 4, 2009; DOI 10.1182/blood-2009-03-212225.
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 CrossRef
Google Scholar
Right arrow Articles by Bonadies, N.
Right arrow Articles by Mueller, B. U.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bonadies, N.
Right arrow Articles by Mueller, B. U.
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  |  Next Article next article arrow

Submitted March 20, 2009; accepted September 28, 2009.

Heterozygous deletion of the PU.1 locus in human AML

Nicola Bonadies1, Thomas Pabst2 and Beatrice U. Mueller1,3

1 Department of Internal Medicine and Clinical Research, University Hospital Berne and University Berne, Berne, Switzerland; 2 Department of Medical Oncology, University Hospital Berne, Switzerland

* Corresponding author; email: beatrice.mueller{at}insel.ch

Abstract

The transcription factor PU.1 is essential for myeloid development. Targeted disruption of an upstream regulatory element (URE) decreases PU.1 expression by 80% and leads to AML in mice. Here, we sequenced the URE sequences of PU.1 in 120 AML patients. Four polymorphisms (SNP) in the URE were observed, with homozygosity in all SNPs in 37 patients. Among them, we compared samples at diagnosis and remission, and one patient with cytogenetically normal AML-M2 was identified with heterozygosity in three of the SNPs in the URE at remission. Loss of heterozygosity (LOH) was further found in this patient at two polymorphic sites in the 5' promoter region and in two intronic sites flanking exon 4, thus suggesting LOH covering at least 40kb of the PU.1-locus. Consistently, PU.1 expression in this patient was markedly reduced. Our study suggests that heterozygous deletion of the PU.1 locus can be associated with human AML.


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?




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020