SEARCH:   Advanced

Blood, 15 June 2007, Vol. 109, No. 12, pp. 5079-5086. Prepublished online as a Blood First Edition Paper on March 9, 2007; DOI 10.1182/blood-2007-02-071225. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-02-071225v1 109/12/5079    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 Raveche, E. S. Articles by Marti, G. E. Search for Related Content PubMed PubMed Citation Articles by Raveche, E. S. Articles by Marti, G. E. Related Collections Free Research Articles Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice Elizabeth S. Raveche1, Erica Salerno1, Brian J. Scaglione1, Vijaya Manohar2, Fatima Abbasi3, Yi-Chu Lin1, Torgny Fredrickson4, Pablo Landgraf7, Sumant Ramachandra1, Konrad Huppi5, Jorge R. Toro6, Vincent E. Zenger3, Robert A. Metcalf3, and Gerald E. Marti3 1 Department of Pathology and Lab Medicine, University of Medicine and Dentistry New Jersey/New Jersey Medical School, Newark, NJ; 2 Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC; 3 Center for Biologics Evaluation and Research/Food and Drug Administration, Bethesda, MD; 4 Laboratory of Immunopathology, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD; 5 Gene Silencing Section, Advanced Technology Center/National Cancer Institute (NCI), National Institutes of Health, Gaithersburg, MD; 6 Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD; 7 Laboratory of RNA Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY New Zealand black (NZB) mice with autoimmune and B lymphoproliferative disease (B-LPD) are a model for human chronic lymphocytic leukemia (CLL). A genomewide linkage scan of the NZB loci associated with lymphoma was conducted in F1 backcrosses of NZB and a control strain, DBA/2. Of 202 mice phenotyped for the presence or absence of LPD, surface maker expression, DNA content, and microsatellite polymorphisms, 74 had disease. The CD5+, IgM+, B220dim, hyperdiploid LPD was linked to 3 loci on chromosomes 14, 18, and 19 that are distinct from previously identified autoimmunity-associated loci. The region of synteny with mouse D14mit160 is the human 13q14 region, associated with human CLL, containing microRNAs mir-15a16-1. DNA sequencing of multiple NZB tissues identified a point mutation in the 3' flanking sequence of the identical microRNA, mir-16-1, and this mutation was not present in other strains, including the nearest neighbor, NZW. Levels of miR-16 were decreased in NZB lymphoid tissue. Exogenous miR-16 delivered to an NZB malignant B-1 cell line resulted in cell-cycle alterations and increased apoptosis. Linkage of the mir-15a/16-1 complex and the development of B-LPD in this spontaneous mouse model suggest that the altered expression of the mir-15a/16-1 is the molecular lesion in CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: MicroRNAs play a role in neoplasia Thomas J. Kipps Blood 2007 109: 5071-5072. [Full Text] [PDF] This article has been cited by other articles: G. A. Calin, A. Cimmino, M. Fabbri, M. Ferracin, S. E. Wojcik, M. Shimizu, C. Taccioli, N. Zanesi, R. Garzon, R. I. Aqeilan, et al. MiR-15a and miR-16-1 cluster functions in human leukemia PNAS, April 1, 2008; 105(13): 5166 - 5171. [Abstract] [Full Text] [PDF] T. J. Kipps Chronic Lymphocytic Leukemia: Prognostic Markers and Revised Criteria for Treatment and Response Assessment ASCO Educational Book, January 1, 2008; 2008(1): 286 - 290. [Abstract] [Full Text] [PDF] W. Zhang, J. E. Dahlberg, and W. Tam MicroRNAs in Tumorigenesis: A Primer Am. J. Pathol., September 1, 2007; 171(3): 728 - 738. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020