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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-12-3904. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3904v1 101/11/4298    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 Mundschau, G. Articles by Crispino, J. D. Search for Related Content PubMed PubMed Citation Articles by Mundschau, G. Articles by Crispino, J. D. Related Collections Hematopoiesis and Stem Cells Neoplasia Brief Reports Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4298-4300 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Brief report Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis Gina Mundschau, Sandeep Gurbuxani, Alan S. Gamis, Marianne E. Greene, Robert J. Arceci, and John D. Crispino From the Ben May Institute for Cancer Research, University of Chicago, IL; the Section of Hematology/Oncology/Blood and Marrow Transplantation, Children's Mercy Hospital and Clinics, Kansas City, MO; and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. As many as 10% of infants with Down syndrome (DS) present with transient myeloproliferative disorder (TMD) at or shortly after birth. TMD is characterized by an abundance of blasts within the peripheral blood and liver, and notably undergoes spontaneous remission in the majority of cases. TMD may be a precursor to acute megakaryoblastic leukemia (AMKL), with an estimated 30% of TMD patients developing AMKL within 3 years. We recently reported that mutations in the transcription factor GATA1 are associated with DS-AMKL. To determine whether the acquisition of GATA1 mutations is a late event restricted to acute leukemia, we analyzed GATA1 in DNA from TMD patients. Here we report that GATA1 is mutated in the TMD blasts from every infant examined. These results demonstrate that GATA1 is likely to play a critical role in the etiology of TMD, and mutagenesis of GATA1 represents a very early event in DS myeloid leukemogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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