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Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-02-0558. This Article Full Text (PDF) All Versions of this Article: 2002-02-0558v1 100/8/2973    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 Novak, A. J Articles by Jelinek, D. F Search for Related Content PubMed PubMed Citation Articles by Novak, A. J Articles by Jelinek, D. F Social Bookmarking                   What's this? Submitted February 21, 2002 Accepted June 4, 2002 Aberrant expression of B lymphocyte stimulator by B chronic lymphocytic leukemia cells: A mechanism for survival Anne J Novak, Richard J Bram, Neil E Kay, and Diane F Jelinek* Immunology, Mayo Clinic, Rochester, MN, USA Immunology, Mayo Clinic, Rochester, MN, USA; Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA Internal Medicine, Mayo Clinic, Rochester, MN, USA; Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA Immunology, Mayo Clinic, Rochester, MN, USA; Internal Medicine, Mayo Clinic, Rochester, MN, USA * Corresponding author; email: jelinek.diane{at}mayo.edu. B cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5+ B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and therefore, prolonged survival. B lymphocyte stimulator, BLyS, is a newly identified tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B cell development and homeostasis and it shares significant homology with another TNF superfamily member, APRIL. The striking effects of BLyS on normal B cell maintenance and survival raises the possibility that it may be involved in pathogenesis and maintenance of hematological malignancies, including B-CLL. In this study, we investigated the status of APRIL and BLyS expression, as well as their receptors, in this disease. All B-CLL patient cells studied expressed one or more of three known receptors for BLyS; however, the pattern of expression was variable. In addition, we demonstrate for the first time that B-CLL cells from a subset of patients aberrantly express BLyS and APRIL mRNA while these molecules were not detectable in normal B cells. Furthermore, we provide in vitro evidence that BLyS protects B-CLL cells from apoptosis and enhances cell survival. Because these molecules are key regulators of B cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Gupta, S. R. Dillon, S. C. Ziesmer, A. L. Feldman, T. E. Witzig, S. M. Ansell, J. R. Cerhan, and A. J. Novak A proliferation-inducing ligand mediates follicular lymphoma B-cell proliferation and cyclin D1 expression through phosphatidylinositol 3-kinase-regulated mammalian target of rapamycin activation Blood, May 21, 2009; 113(21): 5206 - 5216. [Abstract] [Full Text] [PDF] A. J. Novak, S. L. Slager, Z. S. Fredericksen, A. H. Wang, M. M. Manske, S. Ziesmer, M. Liebow, W. R. Macon, S. R. Dillon, T. E. Witzig, et al. 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