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

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 15 August 2004, Vol. 104, No. 4, pp. 1127-1136.
Prepublished online as a Blood First Edition Paper on April 20, 2004; DOI 10.1182/blood-2003-10-3550.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2003-10-3550v1
104/4/1127    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 Gurevich, R. M.
Right arrow Articles by Humphries, R. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gurevich, R. M.
Right arrow Articles by Humphries, R. K.
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

NUP98-Topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation

Rhonna M. Gurevich, Peter D. Aplan, and R. Keith Humphries

From the Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; National Cancer Institute, National Naval Medical Center, Bethesda, MD; and the Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

Chromosomal rearrangements of the 11p15 locus have been identified in hematopoietic malignancies, resulting in translocations involving the N-terminal portion of the nucleoporin gene NUP98. Fifteen different fusion partner genes have been identified for NUP98, and more than one half of these are homeobox transcription factors. By contrast, the NUP98 fusion partner in t(11;20) is Topoisomerase I (TOP1), a catalytic enzyme recognized for its key role in relaxing supercoiled DNA. We now show that retrovirally engineered expression of NUP98-TOP1 in murine bone marrow confers a potent in vitro growth advantage and a block in differentiation in hematopoietic precursors, evidenced by a competitive growth advantage in liquid culture, increased replating efficient of colony-forming cells (CFCs), and a marked increase in spleen colony-forming cell output. Moreover, in a murine bone marrow transplantation model, NUP98-TOP1 expression led to a lethal, transplantable leukemia characterized by extremely high white cell counts, splenomegaly, and mild anemia. Strikingly, a mutation to a TOP1 site to inactivate the isomerase activity essentially left unaltered the growth-promoting and leukemogenic effects of NUP98-TOP1. These findings, together with similar biologic effects reported for NUP98-HOX fusions, suggest unexpected, overlapping functions of NUP98 fusion genes, perhaps related to common DNA binding properties. (Blood. 2004;104:1127-1136)


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
 BloodHome page
D. Jankovic, P. Gorello, T. Liu, S. Ehret, R. La Starza, C. Desjobert, F. Baty, M. Brutsche, P.-S. Jayaraman, A. Santoro, et al.
Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia
Blood, June 15, 2008; 111(12): 5672 - 5682.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Heuser, B. Argiropoulos, F. Kuchenbauer, E. Yung, J. Piper, S. Fung, R. F. Schlenk, K. Dohner, T. Hinrichsen, C. Rudolph, et al.
MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML
Blood, September 1, 2007; 110(5): 1639 - 1647.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X.-T. Bai, B.-W. Gu, T. Yin, C. Niu, X.-D. Xi, J. Zhang, Z. Chen, and S.-J. Chen
Trans-Repressive Effect of NUP98-PMX1 on PMX1-Regulated c-FOS Gene through Recruitment of Histone Deacetylase 1 by FG Repeats.
Cancer Res., May 1, 2006; 66(9): 4584 - 4590.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
P. Klener, M. Szynal, Y. Cleuter, M. Merimi, H. Duvillier, F. Lallemand, C. Bagnis, P. Griebel, C. Sotiriou, A. Burny, et al.
Insights into Gene Expression Changes Impacting B-Cell Transformation: Cross-Species Microarray Analysis of Bovine Leukemia Virus Tax-Responsive Genes in Ovine B Cells
J. Virol., February 15, 2006; 80(4): 1922 - 1938.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Nebral, H. H. Schmidt, O. A. Haas, and S. Strehl
NUP98 Is Fused to Topoisomerase (DNA) II{beta} 180 kDa (TOP2B) in a Patient with Acute Myeloid Leukemia with a New t(3;11)(p24;p15)
Clin. Cancer Res., September 15, 2005; 11(18): 6489 - 6494.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020