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Blood, 1 July 2005, Vol. 106, No. 1, pp. 296-303. Prepublished online as a Blood First Edition Paper on March 8, 2005; DOI 10.1182/blood-2005-01-0034. This Article Full Text (PDF) Supplemental Figures and Worksheet All Versions of this Article: 2005-01-0034v1 106/1/296    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 Bergsagel, P L Articles by Shaughnessy, Jr, J. Search for Related Content PubMed PubMed Citation Articles by Bergsagel, P L Articles by Shaughnessy, Jr, J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 6, 2005 Accepted February 27, 2005 Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma P L Bergsagel, W M Kuehl*, Fenghuang Zhan, Jeffrey Sawyer, Bart Barlogie, and John Shaughnessy, Jr Comprehensive Cancer Center and Division of Hematology-Oncology, Mayo Clinic Scottsdale, Scottsdale, AZ, USA Genetics Branch, National Cancer Institute, Bethesda, MD, USA Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics, University of Arkansas for Medical Sciences, Little Rock, AR, USA * Corresponding author; email: wmk{at}helix.nih.gov. Two oncogenic pathways have been hypothesized for multiple myeloma (MM) and pre-malignant MGUS tumors: a non-hyperdiploid pathway associated with a high prevalence of IgH translocations; and a hyperdiploid pathway associated with multiple trisomies of eight chromosomes. Cyclin D1, D2, or D3 expression appears to be increased and/or dysregulated in virtually all MM tumors despite their low proliferative capacity. Translocations can directly dysregulate CCND1 (11q13) or CCND3 (6p21), or MAF (16q23) or MAFB (20q11) transcription factors that target CCND2. Bi-allelic dysregulation of CCND1 occurs in nearly 40% of tumors, most of which are hyperdiploid. Other tumors express increased CCND2, either with or without a t(4;14) translocation. Using gene expression profiling to identify five recurrent translocations, specific trisomies, and expression of cyclin D genes, MM tumors can be divided into eight TC (translocation/cyclin D) groups - 11q13, 6p21, 4p16, maf, D1, D1+D2, D2, and NONE - that appear to be defined by early, and perhaps initiating, oncogenic events. However, despite subsequent progression events, these groups have differing gene expression profiles, and also significant differences in the prevalence of bone disease, frequency at relapse, and progression to extramedullary tumor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Multiple myeloma: all roads lead to cyclin D Bruno Quesnel Blood 2005 106: 1-2. [Full Text] [PDF] This article has been cited by other articles: L. Chiecchio, G. P. Dagrada, R. K.M. Protheroe, D. M. Stockley, A. G. Smith, K. H. Orchard, N. C.P. Cross, C. J. Harrison, F. M. 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