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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4232-4236. Prepublished online as a Blood First Edition Paper on August 29, 2006; DOI 10.1182/blood-2006-05-025148. This Article Full Text (PDF) All Versions of this Article: blood-2006-05-025148v1 108/13/4232    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 Inoue, N. Articles by Kinoshita, T. Search for Related Content PubMed PubMed Citation Articles by Inoue, N. Articles by Kinoshita, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 23, 2006 Accepted August 8, 2006 Molecular basis of clonal expansion of hematopoiesis in two patients with paroxysmal nocturnal hemoglobinuria (PNH) Norimitsu Inoue, Tomohisa Izui-Sarumaru, Yoshiko Murakami, Yuichi Endo, Jun-Ichi Nishimura, Ken Kurokawa, Maki Kuwayama, Hiroaki Shime, Takashi Machii, Yuzuru Kanakura, Gabrielle Meyers, Carl Wittwer, Zhong Chen, William Babcock, Debra Frei-Lahr, Charles J. Parker, and Taroh Kinoshita* Department of Molecular Genetics, Osaka Medical Center for Cancer, Osaka, Japan Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Japan Research Institute for Microbial Diseases, Osaka University, Japan Research Institute for Microbial Diseases, Osaka University Department of Medicine, Duke University Medical Center, Durham, NC, USA Genome Information Research Center, Osaka University, Osaka, Japan Osaka University/Osaka University School of Medicine, Osaka, Japan Department of Hematology and Oncology, Osaka University School of Medicine, Osaka, Japan University of Utah School of Medicine/George E. Whalen VA Medical Center, Salt Lake City, Utah, USA Department of Pathalogy, University of Utah School of Medicine, Salt Lake City, Utah, USA Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA Department of Medicine, Division of Hematology/Oncology, Baptist Medical Center, Columbia, SC, USA Department of Medicine, Division of Hematology, Medical University of South Carolina, SC, USA Osaka University, Osaka, Japan/Japan Science and Technology Agency, Saitama, Japan * Corresponding author; email: tkinoshi{at}biken.osaka-u.ac.jp. Somatic mutation of PIGA in hematopoietic stem cells causes deficiency of glycosyl phosphatidylinositol-anchored proteins in paroxysmal nocturnal hemoglobinuria (PNH) that underlies the intravascular hemolysis but does not account for expansion of the PNH clone. Immune mechanisms may mediate clonal selection but appear insufficient to account for the clonal dominance necessary for PNH to become clinically apparent. Herein we report two PNH patients whose PIGA-mutant cells had a concurrent, acquired rearrangement of chromosome 12. In both cases, der(12) had a break within the 3' untranslated region of HMGA2, the architectural transcription factor gene deregulated in many benign mesenchymal tumors, that caused ectopic expression of HMGA2 in the bone marrow. These observations suggest that aberrant HMGA2 expression, in concert with mutant PIGA, accounts for clonal hematopoiesis in these two patients and suggest the concept of PNH as a benign tumor of the bone marrow. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: How many mutations does it take to get PNH? Wendell F. Rosse Blood 2006 108: 3960-3961. [Full Text] [PDF] This article has been cited by other articles: D. Dingli, L. Luzzatto, and J. M. Pacheco Neutral evolution in paroxysmal nocturnal hemoglobinuria PNAS, November 25, 2008; 105(47): 18496 - 18500. [Abstract] [Full Text] [PDF] H. Bruchova, M. Merkerova, and J. T. Prchal Aberrant expression of microRNA in polycythemia vera Haematologica, July 1, 2008; 93(7): 1009 - 1016. [Abstract] [Full Text] [PDF] R. A. Brodsky Narrative Review: Paroxysmal Nocturnal Hemoglobinuria: The Physiology of Complement-Related Hemolytic Anemia Ann Intern Med, April 15, 2008; 148(8): 587 - 595. [Full Text] [PDF] R. A. Brodsky Paroxysmal Nocturnal Hemoglobinuria: Stem Cells and Clonality Hematology, January 1, 2008; 2008(1): 111 - 115. [Abstract] [Full Text] [PDF] L. Gargiulo, S. Lastraioli, G. Cerruti, M. Serra, F. Loiacono, S. Zupo, L. Luzzatto, and R. Notaro Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria Blood, June 1, 2007; 109(11): 5036 - 5042. [Abstract] [Full Text] [PDF] C. Mayr, M. T. Hemann, and D. P. Bartel Disrupting the Pairing Between let-7 and Hmga2 Enhances Oncogenic Transformation Science, March 16, 2007; 315(5818): 1576 - 1579. [Abstract] [Full Text] [PDF]

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