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, 12 February 2009, Vol. 113, No. 7, pp. 1522-1525.
Prepublished online as a Blood First Edition Paper on December 5, 2008; DOI 10.1182/blood-2008-03-143321.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Tables and Figures
Right arrow All Versions of this Article:
blood-2008-03-143321v1
113/7/1522    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 CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zeuner, A.
Right arrow Articles by De Maria, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zeuner, A.
Right arrow Articles by De Maria, R.
Related Collections
Right arrow Myeloid Neoplasia
Right arrow Red Cells, Iron, and Erythropoiesis
Right arrow Brief Reports
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

MYELOID NEOPLASIA

Brief report

Activity of the BH3 mimetic ABT-737 on polycythemia vera erythroid precursor cells

Ann Zeuner1, Francesca Pedini1, Federica Francescangeli1, Michele Signore1, Gabriella Girelli2, Agostino Tafuri2, and Ruggero De Maria1

1 Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy; and 2 Department of Cellular Biotechnology and Hematology, University La Sapienza, Rome, Italy

An increased expression of antiapoptotic molecules is often found in malignant cells, where it contributes to their clonal expansion by conferring an improved survival ability. We found that erythroid precurors derived from patients with polycythemia vera (PV) with medium and high JAK2V617F mutation rates often express elevated levels of the antiapoptotic molecules Bcl-2 and Bcl-XL (5 of 12 patients with 3 to 7 times Bcl-2 and 3 of 12 patients with 4 to 7 times Bcl-XL than average normal controls) and are more resistant to myelosuppressive drugs than normal erythroblasts. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-XL, and Bcl-W, induced apoptosis preferentially in JAK2V617F-high PV erythroid precursors as compared with JAK2V617F-low or normal erythroblasts. ABT-737 inhibited also the proliferation of PV erythroblasts and interfered with the formation of endogenous erythroid colonies by PV hematopoietic progenitors. Altogether, these results suggest that small-molecule inhibitors of Bcl-2/Bcl-XL may be used in the treatment of patients with PV with high JAK2V617F allele burden.


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