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This Article Full Text Full Text (PDF) 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 Mueller, B. U. Articles by Tenen, D. G. Search for Related Content PubMed PubMed Citation Articles by Mueller, B. U. Articles by Tenen, D. G. Related Collections Neoplasia Gene Expression Related Letters in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2002, Vol. 100, No. 3, pp. 998-1007 NEOPLASIA Heterozygous PU.1 mutations are associated with acute myeloid leukemia Beatrice U. Mueller, Thomas Pabst, Motomi Osato, Norio Asou, Lisa M. Johansen, Mark D. Minden, Gerhard Behre, Wolfgang Hiddemann, Yoshiaki Ito, and Daniel G. Tenen From the Harvard Institutes of Medicine, Harvard Medical School, Boston, MA; the Department of Internal Medicine, Kumamoto University, Japan; the Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto, Japan; the Department of Medicine and Medical Biophysics, University of Toronto, Canada; the Department of Medicine III, Grosshadern, Clinical Cooperative Group Acute Myeloid Leukemia of the National Research Center for Environment and Health (GSF), Munich, Germany. The transcription factor PU.1 is required for normal blood cell development. PU.1 regulates the expression of a number of crucial myeloid genes, such as the macrophage colony-stimulating factor (M-CSF) receptor, the granulocyte colony-stimulating factor (G-CSF) receptor, and the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor. Myeloid cells derived from PU.1/ mice are blocked at the earliest stage of myeloid differentiation, similar to the blast cells that are the hallmark of human acute myeloid leukemia (AML). These facts led us to hypothesize that molecular abnormalities involving the PU.1 gene could contribute to the development of AML. We identified 10 mutant alleles of the PU.1 gene in 9 of 126 AML patients. The PU.1 mutations comprised 5 deletions affecting the DNA-binding domain, and 5 point mutations in 1) the DNA-binding domain (2 patients), 2) the PEST domain (2 patients), and 3) the transactivation domain (one patient). DNA binding to and transactivation of the M-CSF receptor promoter, a direct PU.1 target gene, were deficient in the 7 PU.1 mutants that affected the DNA-binding domain. In addition, these mutations decreased the ability of PU.1 to synergize with PU.1-interacting proteins such as AML1 or c-Jun in the activation of PU.1 target genes. This is the first report of mutations in the PU.1 gene in human neoplasia and suggests that disruption of PU.1 function contributes to the block in differentiation found in AML patients. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letters in Blood Online: Are PU.1 mutations frequent genetic events in acute myeloid leukemia (AML)? Charlotte Lamandin, Christophe Sagot, Christophe Roumier, Pascale Lepelley, Stéphane De Botton, Alain Cosson, Pierre Fenaux, and Claude Preudhomme Blood 2002 100: 4680. [Full Text] [PDF] Heterozygous PU.1 mutations are associated with acute myeloid leukemia Beatrice U. Mueller, Thomas Pabst, Motomi Osato, Norio Asou, Lisa M. Johansen, Mark D. Minden, Gerhard Behre, Wolfgang Hiddemann, Yoshiaki Ito, and Daniel G. Tenen Blood 2003 101: 2074. [Full Text] [PDF] This article has been cited by other articles: F. P.G. Silva, I. Almeida, B. Morolli, G. Brouwer-Mandema, H. 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