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, 15 May 2008, Vol. 111, No. 10, pp. 4930-4933.
Prepublished online as a Blood First Edition Paper on February 27, 2008; DOI 10.1182/blood-2008-01-117770.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2008-01-117770v1
111/10/4930    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 Meshinchi, S.
Right arrow Articles by Radich, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meshinchi, S.
Right arrow Articles by Radich, J. P.
Related Collections
Right arrow Neoplasia
Right arrow Brief Reports
Right arrow Clinical Trials and Observations
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

Brief Report

Structural and numerical variation of FLT3/ITD in pediatric AML

Soheil Meshinchi13, Derek L. Stirewalt1,4, Todd A. Alonzo3,5, Titus J. Boggon6, Robert B. Gerbing3, Jennifer L. Rocnik7, Beverly J. Lange3,6, D. Gary Gilliland7, and Jerald P. Radich1,4

1 Clinical Research Division, Fred Hutchinson Cancer Research Center, and 2 Department of Pediatrics, University of Washington Medical Center, Seattle; 3 Children's Oncology Group, Arcadia, CA; 4 Department of Medicine, University of Washington Medical Center, Seattle; 5 University of Southern California Keck School of Medicine, Los Angeles; 6 Department of Pharmacology, Yale University School of Medicine, New Haven, CT; and 7 Division of Hematology/Oncology, Department of Pathology, Brigham and Women's Hospital; the Howard Hughes Medical Institute, Harvard Medical School, Boston, MA

FLT3 internal tandem duplication (FLT3/ITD) is a common somatic mutation in acute myeloid leukemia (AML) with significant variation in the position, length, and number of duplications of the FLT3 gene. We evaluated these physical characteristics in FLT3/ITD-positive patients who were treated on CCG-2941/2961 and correlated them with clinical outcome. Fiftynine of 77 FLT3/ITD-positive patients (77%) had a single ITD, 16 (21%) had 2 ITDs, and 2 (3%) had 3 ITDs. The length of the duplicated region varied from 6 to 51 amino acids, and in all cases amino acid residues Y591–Y597 were duplicated. Structural analysis demonstrated that Y591–Y597 encodes the switch and zipper regions of the juxtamembrane domain of FLT3. In addition, 24 of 77 patients (31%) had duplication of the critical STAT5 docking sites Y589/591. Patients with longer ITDs had a worse relapse-free survival (19% vs 51%, P = .035), while the presence of more than 1 ITD was not clinically significant. Physical characteristics including the length of FLT3/ITD may influence FLT3 activation state by altering its structure and may impact response to therapy.


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
S. Kayser, R. F. Schlenk, M. C. Londono, F. Breitenbuecher, K. Wittke, J. Du, S. Groner, D. Spath, J. Krauter, A. Ganser, et al.
Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome
Blood, September 17, 2009; 114(12): 2386 - 2392.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Meshinchi and F. R. Appelbaum
Structural and Functional Alterations of FLT3 in Acute Myeloid Leukemia
Clin. Cancer Res., July 1, 2009; 15(13): 4263 - 4269.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
I. H. I. M. Hollink, M. M. van den Heuvel-Eibrink, M. Zimmermann, B. V. Balgobind, S. T. C. J. M. Arentsen-Peters, M. Alders, A. Willasch, G. J. L. Kaspers, J. Trka, A. Baruchel, et al.
Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia
Blood, June 4, 2009; 113(23): 5951 - 5960.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020