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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2480-2489. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-10-3383. This Article Full Text (PDF) All Versions of this Article: 2003-10-3383v1 103/7/2480    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ahmed, M. Articles by Vyas, P. Search for Related Content PubMed PubMed Citation Articles by Ahmed, M. Articles by Vyas, P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted October 2, 2003 Accepted November 21, 2003 Natural history of GATA1 mutations in Down Syndrome Momin Ahmed, Alexander Sternberg, Georgina Hall, Angela Thomas, Owen Smith, Aengus O'Marcaigh, Robert Wynn, Richard Stevens, Michael Addison, Derek King, Barbara Stewart, Brenda Gibson, Irene Roberts, and Paresh Vyas* Department of Hematology and MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom Department of Pediatric Hematology, Royal Hospital for Sick Children, Edinburgh, United Kingdom Department of Pediatric Hematology, Our Lady Hospital for Sick Children, Dublin, Ireland Departments of Pediatric Hematology and Clinical Biochemistry, Royal Manchester Children's University Hospital, Manchester, United Kingdom Department of Pediatric Hematology, Aberdeen Children's Hospital, Aberdeen, United Kingdom Department of Community Pediatrics, Oxford Radcliffe Hospital NHS Trust, Oxford, United Kingdom Department of Hematology, Royal Hospital for Sick Children Yorkhill Hospital NHS Trust, Glasgow, United Kingdom Department of Hematology, Hammersmith Hospital, Imperial College, London, United Kingdom * Corresponding author; email: paresh.vyas{at}imm.ox.ac.uk. Acquired mutations in megakaryocyte transcription factor GATA1 have recently been reported in Down Syndrome (DS) Transient Myeloproliferative Disorder (TMD) and Acute Megakaryoblastic Leukemia (AMKL). To provide novel insight into GATA1 mutations in DS, genomic DNA was assayed from: 12 AMKL and 4 TMD cases (including neonatal, pre-diagnosis samples in 4/16), neonatal blood spots from 21 DS children without clinically-evident TMD or AMKL and 62 non-DS cord blood samples, using techniques not previously employed with such samples. GATA1 mutations were present in all TMD and AMKL cases and at birth in 3/4 children without known clinical TMD, who later developed AMKL. They were present at birth in 2/21 DS neonates, who have not yet, but could still, develop AMKL (now 26 and 31 months). GATA1 mutations were not detected in 62 non-DS cord blood samples. In 4 AMKL patients multiple independent GATA1 mutations were observed. These data show GATA1 mutations occur in utero in most DS TMD and AMKL, that they may occur without clinical signs of disease and that multiple separate GATA1-mutant clones can occur in an individual. The findings have implications for pathogenesis of DS TMD and AMKL and highlight parallels between DS AMKL and other childhood leukemias. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Down syndrome and leukemia—it's in the cards Jeffrey W. Taub Blood 2004 103: 2434. [Full Text] [PDF] This article has been cited by other articles: A. C. Xavier, Y. Ge, and J. W. Taub Down Syndrome and Malignancies: A Unique Clinical Relationship: A Paper from the 2008 William Beaumont Hospital Symposium on Molecular Pathology J. Mol. Diagn., September 1, 2009; 11(5): 371 - 380. [Abstract] [Full Text] [PDF] R. Shimizu, E. Kobayashi, J. D. Engel, and M. 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