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Blood, 16 April 2009, Vol. 113, No. 16, pp. 3754-3764. Prepublished online as a Blood First Edition Paper on December 1, 2008; DOI 10.1182/blood-2008-10-184077. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-10-184077v1 113/16/3754    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 Malumbres, R. Articles by Lossos, I. S. Search for Related Content PubMed PubMed Citation Articles by Malumbres, R. Articles by Lossos, I. S. Related Collections Immunobiology Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Differentiation stage–specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas Raquel Malumbres1, Kristopher A. Sarosiek1, Elena Cubedo1, Jose W. Ruiz1, Xiaoyu Jiang1, Randy D. Gascoyne2, Robert Tibshirani3, and Izidore S. Lossos1 1 Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, FL; 2 Department of Pathology, British Columbia Cancer Agency, Vancouver, BC; and 3 Departments of Health Research & Policy and Statistics, Stanford University, CA miRNAs are small RNA molecules binding to partially complementary sites in the 3'-UTR of target transcripts and repressing their expression. miRNAs orchestrate multiple cellular functions and play critical roles in cell differentiation and cancer development. We analyzed miRNA profiles in B-cell subsets during peripheral B-cell differentiation as well as in diffuse large B-cell lymphoma (DLBCL) cells. Our results show temporal changes in the miRNA expression during B-cell differentiation with a highly unique miRNA profile in germinal center (GC) lymphocytes. We provide experimental evidence that these changes may be physiologically relevant by demonstrating that GC-enriched hsa-miR-125b down-regulates the expression of IRF4 and PRDM1/BLIMP1, and memory B cell–enriched hsa-miR-223 down-regulates the expression of LMO2. We further demonstrate that although an important component of the biology of a malignant cell is inherited from its nontransformed cellular progenitor—GC centroblasts—aberrant miRNA expression is acquired upon cell transformation. A 9-miRNA signature was identified that could precisely differentiate the 2 major subtypes of DLBCL. Finally, expression of some of the miRNAs in this signature is correlated with clinical outcome of uniformly treated DLBCL patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. M. C. Ohlsson Teague, C. G. Print, and M. L. Hull The role of microRNAs in endometriosis and associated reproductive conditions Hum. Reprod. Update, September 22, 2009; (2009) dmp034v1. [Abstract] [Full Text] [PDF] W. Tam Micro-classifying diffuse large B-cell lymphomas Blood, June 25, 2009; 113(26): 6506 - 6507. [Full Text] [PDF] C. Li, S.-W. Kim, D. Rai, A. R. Bolla, S. Adhvaryu, M. C. Kinney, R. S. Robetorye, and R. C. T. Aguiar Copy number abnormalities, MYC activity, and the genetic fingerprint of normal B cells mechanistically define the microRNA profile of diffuse large B-cell lymphoma Blood, June 25, 2009; 113(26): 6681 - 6690. [Abstract] [Full Text] [PDF]

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