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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4503-4506. Prepublished online as a Blood First Edition Paper on September 23, 2008; DOI 10.1182/blood-2008-05-157859. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-05-157859v1 112/12/4503    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Chou, S. T. Articles by Weiss, M. J. Search for Related Content PubMed PubMed Citation Articles by Chou, S. T. Articles by Weiss, M. J. Related Collections Hematopoiesis and Stem Cells Brief Reports Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Brief Report Trisomy 21 enhances human fetal erythro-megakaryocytic development Stella T. Chou1,2, Joanna B. Opalinska1, Yu Yao1, Myriam A. Fernandes1, Anna Kalota3, John S. J. Brooks4, John K. Choi5, Alan M. Gewirtz3, Gwenn-ael Danet-Desnoyers3, Richard L. Nemiroff6, and Mitchell J. Weiss1,2 1 Division of Hematology, The Children's Hospital of Philadelphia, PA; 2 Department of Pediatrics, and 3 Division of Hematology/Oncology, The University of Pennsylvania School of Medicine, Philadelphia; 4 Department of Pathology, Pennsylvania Hospital, Philadelphia; 5 Department of Pathology, The Children's Hospital of Philadelphia, PA; and 6 Department of Obstetrics and Gynecology, The University of Pennsylvania School of Medicine, Philadelphia Children with Down syndrome exhibit 2 related hematopoietic diseases: transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL). Both exhibit clonal expansion of blasts with biphenotypic erythroid and megakaryocytic features and contain somatic GATA1 mutations. While altered GATA1 inhibits erythro-megakaryocytic development, less is known about how trisomy 21 impacts blood formation, particularly in the human fetus where TMD and AMKL originate. We used in vitro and mouse transplantation assays to study hematopoiesis in trisomy 21 fetal livers with normal GATA1 alleles. Remarkably, trisomy 21 progenitors exhibited enhanced production of erythroid and megakaryocytic cells that proliferated excessively. Our findings indicate that trisomy 21 itself is associated with cell-autonomous expansion of erythro-megakaryocytic progenitors. This may predispose to TMD and AMKL by increasing the pool of cells susceptible to malignant transformation through acquired mutations in GATA1 and other cooperating genes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    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: 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] 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] 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] 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]

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