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Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2003-03-0989. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0989v1 102/6/2146    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 Deaglio, S. Articles by Malavasi, F. Search for Related Content PubMed PubMed Citation Articles by Deaglio, S. Articles by Malavasi, F. Related Collections Immunobiology Neoplasia Signal Transduction Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2146-2155 IMMUNOBIOLOGY CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells Silvia Deaglio, Andrea Capobianco, Luciana Bergui, Jan Dürig, Fortunato Morabito, Ulrich Dührsen, and Fabio Malavasi From the Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, Research Center on Experimental Medicine (CeRMS), and the Department of Medicine and Experimental Oncology, University of Torino Medical School, Italy; Department of Hematology, University Hospital, Essen, Germany; and Bone Marrow Transplant Center, "Bianchi Melacrino Morelli" Hospital, Reggio Calabria, Italy. The prognosis for patients with B-cell chronic lymphocytic leukemia (B-CLL) is generally less favorable for those expressing CD38. Our working hypothesis is that CD38 is not merely a marker in B-CLL, but that it plays a receptor role with pathogenetic potential ruling the proliferation of the malignant clone. CD38 levels were generally low in the patients examined and monoclonal antibody (mAb) ligation was inefficient in signaling. Other cellular models indicated that molecular density and surface organization are critical for CD38 functionality. Interleukin 2 (IL-2) induced a marked up-modulation and surface rearrangement of CD38 in all the patients studied. On reaching a specific expression threshold, CD38 becomes an efficient receptor in purified B-CLL cells. Indeed, mAb ligation is followed by Ca2+ fluxes and by a markedly increased proliferation. The unsuitability of CD38 to perform as a receptor is obviated through close interaction with the B-cell–receptor (BCR) complex and CD19. On mAb binding, CD38 translocates to the membrane lipid microdomains, as shown by a colocalization with the GM1 ganglioside and with CD81, a raft-resident protein. Finally, CD38 signaling in IL-2–treated B-CLL cells prolonged survival and induced the appearance of plasmablasts, providing a pathogenetic hypothesis for the occurrence of Richter syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: CD38 on B-cell chronic lymphocytic leukemia cells has higher expression in lymph nodes than in peripheral blood or bone marrow Ozren Jaksic, Mirjana Mariana Kardum Paro, Ika Kardum Skelin, Rajko Kusec, Vlatko Pejsa, and Branimir Jaksic Blood 2004 103: 1968-1969. [Full Text] [PDF] This article has been cited by other articles: F. Malavasi, S. Deaglio, A. Funaro, E. Ferrero, A. L. Horenstein, E. Ortolan, T. Vaisitti, and S. 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[Abstract] [Full Text] [PDF] J. D. Johnson, E. L. Ford, E. Bernal-Mizrachi, K. L. Kusser, D. S. Luciani, Z. Han, H. Tran, T. D. Randall, F. E. Lund, and K. S. Polonsky Suppressed insulin signaling and increased apoptosis in CD38-null islets. Diabetes, October 1, 2006; 55(10): 2737 - 2746. [Abstract] [Full Text] [PDF] U. H. Frey, H. Nuckel, L. Sellmann, D. Siemer, R. Kuppers, J. Durig, U. Duhrsen, and W. Siffert The GNAS1 T393C Polymorphism Is Associated with Disease Progression and Survival in Chronic Lymphocytic Leukemia. Clin. Cancer Res., October 1, 2006; 12(19): 5686 - 5692. [Abstract] [Full Text] [PDF] S. Deaglio, T. Vaisitti, S. Aydin, E. Ferrero, and F. Malavasi In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia Blood, August 15, 2006; 108(4): 1135 - 1144. [Abstract] [Full Text] [PDF] F. E. Lund, H. Muller-Steffner, H. Romero-Ramirez, M. E. 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Amrani CD38 Expression Is Insensitive to Steroid Action in Cells Treated with Tumor Necrosis Factor-{alpha} and Interferon-{gamma} by a Mechanism Involving the Up-Regulation of the Glucocorticoid Receptor beta Isoform Mol. Pharmacol., February 1, 2006; 69(2): 588 - 596. [Abstract] [Full Text] [PDF] E. Ruiz-Ballesteros, M. Mollejo, A. Rodriguez, F. I. Camacho, P. Algara, N. Martinez, M. Pollan, A. Sanchez-Aguilera, J. Menarguez, E. Campo, et al. Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis Blood, September 1, 2005; 106(5): 1831 - 1838. [Abstract] [Full Text] [PDF] S. Deaglio, T. Vaisitti, L. Bergui, L. Bonello, A. L. Horenstein, L. Tamagnone, L. Boumsell, and F. Malavasi CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival Blood, April 15, 2005; 105(8): 3042 - 3050. [Abstract] [Full Text] [PDF] S. Nedellec, Y. Renaudineau, A. Bordron, C. Berthou, N. Porakishvili, P. M. Lydyard, J.-O. Pers, and P. Youinou B Cell Response to Surface IgM Cross-Linking Identifies Different Prognostic Groups of B-Chronic Lymphocytic Leukemia Patients J. Immunol., March 15, 2005; 174(6): 3749 - 3756. [Abstract] [Full Text] [PDF] N. Chiorazzi, K. R. Rai, and M. Ferrarini Chronic Lymphocytic Leukemia N. Engl. J. Med., February 24, 2005; 352(8): 804 - 815. [Full Text] [PDF] S. Deaglio, T. Vaisitti, and F. Malavasi CD38 Ligation in B-Chronic Lymphocytic Leukemia Cells Induces Sequential Tyrosine Phosphorylation of ZAP70, PLC- {gamma}2 and ERK1/2 Proteins. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 959 - 959. [Abstract] [Full Text] O. Tliba, R. A. Panettieri Jr., S. Tliba, T. F. Walseth, and Y. Amrani Tumor Necrosis Factor-{alpha} Differentially Regulates the Expression of Proinflammatory Genes in Human Airway Smooth Muscle Cells by Activation of Interferon-{beta}-Dependent CD38 Pathway Mol. 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