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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 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 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 Harada, H. Articles by Inaba, T. Search for Related Content PubMed PubMed Citation Articles by Harada, H. Articles by Inaba, T. Related Collections Neoplasia Oncogenes and Tumor Suppressors Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 From the Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan; the Department of Hematology/Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan; and the Department of Internal Medicine, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan. 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. The 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 in 26 (23.6%) of 110 patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEBt), and AML following MDS (defined these 3 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 patients with MDS/AML 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 forces of MDS/AML, and these mutations may represent a distinct clinicopathologic-genetic entity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Mutated SHP and AML in leukemias Gen-Sheng Feng Blood 2004 103: 1982-1983. [Full Text] [PDF] This article has been cited by other articles: F. P.G. Silva, I. Almeida, B. Morolli, G. Brouwer-Mandema, H. Wessels, R. Vossen, H. Vrieling, E. W.A. Marijt, P. J.M. Valk, H. C. Kluin-Nelemans, et al. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia Haematologica, November 1, 2009; 94(11): 1546 - 1554. [Abstract] [Full Text] [PDF] O. Kosmider, V. Gelsi-Boyer, M. Cheok, S. Grabar, V. Della-Valle, F. Picard, F. Viguie, B. Quesnel, O. Beyne-Rauzy, E. Solary, et al. 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Molinas Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutation Blood, June 15, 2005; 105(12): 4664 - 4670. [Abstract] [Full Text] [PDF] D. P. Steensma and A. F. List Genetic Testing in the Myelodysplastic Syndromes: Molecular Insights Into Hematologic Diversity Mayo Clin. Proc., May 1, 2005; 80(5): 681 - 698. [Abstract] [PDF] E. J. Houwerzijl, N. R. Blom, J. J. L. van der Want, H. Louwes, M. T. Esselink, J. W. Smit, E. Vellenga, and J. Th. M. de Wolf Increased peripheral platelet destruction and caspase-3-independent programmed cell death of bone marrow megakaryocytes in myelodysplastic patients Blood, May 1, 2005; 105(9): 3472 - 3479. [Abstract] [Full Text] [PDF] J. C. Mulloy, V. Jankovic, M. Wunderlich, R. Delwel, J. Cammenga, O. Krejci, H. Zhao, P. J. M. Valk, B. Lowenberg, and S. D. Nimer AML1-ETO fusion protein up-regulates TRKA mRNA expression in human CD34+ cells, allowing nerve growth factor-induced expansion PNAS, March 15, 2005; 102(11): 4016 - 4021. [Abstract] [Full Text] [PDF] S. Goyama, Y. Yamaguchi, Y. Imai, M. Kawazu, M. Nakagawa, T. Asai, K. Kumano, K. Mitani, S. Ogawa, S. Chiba, et al. The transcriptionally active form of AML1 is required for hematopoietic rescue of the AML1-deficient embryonic para-aortic splanchnopleural (P-Sp) region Blood, December 1, 2004; 104(12): 3558 - 3564. [Abstract] [Full Text] [PDF] D. H. Christiansen, M. K. Andersen, and J. Pedersen-Bjergaard Mutations of AML1 are common in therapy-related myelodysplasia following therapy with alkylating agents and are significantly associated with deletion or loss of chromosome arm 7q and with subsequent leukemic transformation Blood, September 1, 2004; 104(5): 1474 - 1481. [Abstract] [Full Text] [PDF]

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