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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2003-01-0013. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0013v1 101/11/4301    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 Hitzler, J. K. Articles by Zipursky, A. Search for Related Content PubMed PubMed Citation Articles by Hitzler, J. K. Articles by Zipursky, A. Related Collections 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. 4301-4304 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Brief report GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome Johann K. Hitzler, Joseph Cheung, Yue Li, Stephen W. Scherer, and Alvin Zipursky From the Department of Pediatrics, Division of Hematology/Oncology, and the Program in Developmental Biology, Program in Genetics and Genomic Biology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; and the Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada. Children with constitutional trisomy 21 (Down syndrome) have an approximately 500-fold increased risk of developing acute megakaryoblastic leukemia (AMKL), a form of acute myeloid leukemia. Unique to newborn infants with Down syndrome is a transient leukemia (TL), also referred to as transient myeloproliferative syndrome, that undergoes spontaneous remission in the majority of cases but in approximately 20% is followed by AMKL later in life. Recently mutations of the gene encoding the hematopoietic transcription factor GATA1 were shown to be specific for AMKL of Down syndrome. Here, we demonstrate that GATA1 mutations are present in blasts of TL and show the identical GATA1 mutation in sequential samples collected from a patient during TL and subsequent AMKL. These findings suggest a model of malignant transformation in Down syndrome AMKL in which GATA1 mutations are an early event and AMKL arises from latent TL clones following initial apparent remission. 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