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Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2003-02-0390. This Article Full Text (PDF) All Versions of this Article: 2003-02-0390v1 102/8/2960    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 Xu, G. Articles by Ito, E. Search for Related Content PubMed PubMed Citation Articles by Xu, G. Articles by Ito, E. Social Bookmarking                   What's this? Submitted February 6, 2003 Accepted June 1, 2003 Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down's syndrome Gang Xu, Masumi Nagano, Rika Kanezaki, Tsutomu Toki, Yasuhide Hayashi, Takeshi Taketani, Tomohiko Taki, Tetsuo Mitui, Kenichi Koike, Koji Kato, Masue Imaizumi, Isao Sekine, Yasuhiko Ikeda, Ryoji Hanada, Masahiro Sako, Kazuko Kudo, Seiji Kojima, Osamu Ohneda, Masayuki Yamamoto, and Etsuro Ito* Pediatrics, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan Center for TARA and Institute of Basic Science, University Tsukuba, Tsukuba, Ibaragi, Japan Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Pediatrics, Yamagata University School of Medicine, Yamagata, Japan Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan Pediatrics, The First Nagoya Red Cross Hospital, Nagoya, Aichi, Japan Pediatric Hematology and Oncology, Tohoku University School of Medicine, Sendai, Miyagi, Japan Pediatrics, National Defense Medical College, Tokorozawa, Saitama, Japan Pediatrics, Aomori City Hospital, Aomori, Japan Hematology/Oncology, The Saitama Children's Medical Center, Saitama, Japan Pediatrics, Osaka City General Hospital, Osaka, Japan Pediatrics, Nagoya University School of Medicine, Nagoya, Aichi, Japan * Corresponding author; email: eturou{at}cc.hirosaki-u.ac.jp. Transient myeloproliferative disorder (TMD) is a leukemoid reaction occurring occasionally in Down's syndrome newborn infants. Acute megakaryocytic leukemia (AMKL) develops in approximately 20% to 30% of the cases with TMD. Recently, acquired mutations in the N-terminal activation domain of the GATA-1 gene, encoding the erythroid/megakaryocytic transcription factor GATA-1, have been reported in Down's syndrome-related AMKL (DS-AMKL). To understand the multi-step leukemogenesis in Down's syndrome, GATA-1 mutations were investigated in TMD patients. We show here that mutations in the GATA-1 gene were detected in 21 out of 22 cases with TMD. Most of the mutations in TMD were located in the regions including exon 2 and were essentially identical to those observed in DS-AMKL. In the DS-AMKL cell line, MGS, which itself expresses only a truncated mutant of GATA-1, expression of full-length GATA-1 induced the differentiation towards the erythroid lineage. However, expression of the short form of GATA-1 did not induce erythroid differentiation. These results indicate that expression of GATA-1 with a defective N-terminal activation domain contributes to the expansion of TMD blast cells and that other genetic changes contribute to the development of AMKL in Down's syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Hoeller, M. P. Bihl, A. Tzankov, T. Kuehne, C. Potthoff, and E. Bruder New GATA1 mutation in codon 2 leads to the earliest known premature stop codon in transient myeloproliferative disorder Blood, October 22, 2009; 114(17): 3717 - 3718. [Full Text] [PDF] D. C. Cabelof, H. V. Patel, Q. Chen, H. van Remmen, L. H. Matherly, Y. Ge, and J. W. Taub Mutational spectrum at GATA1 provides insights into mutagenesis and leukemogenesis in Down syndrome Blood, September 24, 2009; 114(13): 2753 - 2763. [Abstract] [Full Text] [PDF] S. 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