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 December 2008, Vol. 112, No. 12, pp. 4507-4511.
Prepublished online as a Blood First Edition Paper on August 8, 2008; DOI 10.1182/blood-2008-04-152967.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Methods and Figure
Right arrow All Versions of this Article:
blood-2008-04-152967v1
112/12/4507    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 Tunstall-Pedoe, O.
Right arrow Articles by Roberts, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tunstall-Pedoe, O.
Right arrow Articles by Roberts, I.
Related Collections
Right arrow Hematopoiesis and Stem Cells
Right arrow Neoplasia
Right arrow Brief Reports
Right arrowRelated Article in Blood Online
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

HEMATOPOIESIS AND STEM CELLS

Brief Report

Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations

Oliver Tunstall-Pedoe1, Anindita Roy1, Anastasios Karadimitris1, Josu de la Fuente1, Nicholas M. Fisk2, Phillip Bennett2, Alice Norton3, Paresh Vyas3, and Irene Roberts1

1 Department of Haematology and 2 Institute of Reproductive and Developmental Biology, Imperial College London and Imperial Healthcare NHS Trust, London; and 3 MRC Molecular Haematology Unit and Department of Haematology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom

Down syndrome (DS) children have a high frequency of acute megakaryoblastic leukemia (AMKL) in early childhood. At least 2 in utero genetic events are required, although not sufficient, for DS-AMKL: trisomy 21 (T21) and N-terminal–truncating GATA1 mutations. To investigate the role of T21 in DS-AMKL, we compared second trimester hemopoiesis in DS without GATA1 mutations to gestation-matched normal controls. In all DS fetal livers (FLs), but not marrows, megakaryocyte-erythroid progenitor frequency was increased (55.9% ± 4% vs 17.1% ± 3%, CD34+CD38+ cells; P < .001) with common myeloid progenitors (19.6% ± 2% vs 44.0% ± 7%) and granulocyte-monocyte (GM) progenitors (15.8% ± 4% vs 34.5% ± 9%) commensurately reduced. Clonogenicity of DS-FL versus normal FL CD34+ cells was markedly increased (78% ± 7% vs 15% ± 3%) affecting megakaryocyte-erythroid (~ 7-fold higher) and GM and colony-forming unit–granulocyte, erythrocyte macrophage, megakaryocyte (CFU-GEMM) progenitors. Replating efficiency of CFU-GEMM was also markedly increased. These data indicate that T21 itself profoundly disturbs FL hemopoiesis and they provide a testable hypothesis to explain the increased susceptibility to GATA1 mutations in DS-AMKL and DS-associated transient myeloproliferative disorder.


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?

Related Article in Blood Online:

Trisomy 21 tilts the balance
Shai Izraeli
Blood 2008 112: 4361-4362. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Cancer Res.Home page
S. Salek-Ardakani, G. Smooha, J. de Boer, N. J. Sebire, M. Morrow, L. Rainis, S. Lee, O. Williams, S. Izraeli, and H. J.M. Brady
ERG Is a Megakaryocytic Oncogene
Cancer Res., June 1, 2009; 69(11): 4665 - 4673.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
F. K. Wiseman, K. A. Alford, V. L.J. Tybulewicz, and E. M.C. Fisher
Down syndrome--recent progress and future prospects
Hum. Mol. Genet., April 15, 2009; 18(R1): R75 - R83.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
I. Ganmore, G. Smooha, and S. Izraeli
Constitutional aneuploidy and cancer predisposition
Hum. Mol. Genet., April 15, 2009; 18(R1): R84 - R93.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Malinge, S. Izraeli, and J. D. Crispino
Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome
Blood, March 19, 2009; 113(12): 2619 - 2628.
[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