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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2316-2324. Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2003-09-3074. This Article Full Text (PDF) All Versions of this Article: 2003-09-3074v1 103/6/2316    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 Harada, H. Articles by Inaba, T. Search for Related Content PubMed PubMed Citation Articles by Harada, H. Articles by Inaba, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted September 8, 2003 Accepted November 5, 2003 High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia Hironori Harada*, Yuka Harada, Hiromasa Niimi, Taiichi Kyo, Akiro Kimura, and Toshiya Inaba Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan Department of Hematology/Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan Department of Internal Medicine, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan * Corresponding author; email: herf1{at}hiroshima-u.ac.jp. A high incidence of somatically acquired point mutations in the AML1/RUNX1 gene has been reported in poorly differentiated acute myeloid leukemia (AML, M0) and in radiation-associated and therapy-related myelodysplastic syndrome (MDS) or AML. Vast majority of AML1 mutations identified in these diseases were localized in the amino (N)-terminal region, especially in the DNA-binding Runt homology domain. In this report, we show that AML1 point mutations were found 26 (23.6%) of 110 patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEBt) and AML following MDS (defined these three disease categories as MDS/AML). Among them, 9 (8.2%) mutations occurred in the carboxy (C)-terminal region, which were exclusively found in MDS/AML and were strongly correlated with sporadic MDS/AML. All MDS/AML patients with an AML1 mutation expressed wild type AML1 protein and had a significantly worse prognosis than those without AML1 mutations. Most AML1 mutants lost trans-activation potential, regardless of their DNA binding potential. These data suggested that AML1 point mutation is one of the major driving force of MDS/AML, and these mutations may represent a distinct clinicopathologic-genetic entity. 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