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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3042-3050. Prepublished online as a Blood First Edition Paper on December 21, 2004; DOI 10.1182/blood-2004-10-3873. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-3873v1 105/8/3042    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 Neoplasia Signal Transduction Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival Silvia Deaglio, Tiziana Vaisitti, Luciana Bergui, Lisa Bonello, Alberto L. Horenstein, Luca Tamagnone, Laurence Boumsell, and Fabio Malavasi From the Department of Genetics, Biology and Biochemistry; Research Center on Experimental Medicine (CeRMS); Division of Hematology; and Institute for Cancer Research and Treatment (IRCC); all at the University of Torino Medical School, Torino, Italy; and Faculty of Medicine, Institut National de la Santé etde la Recherche Médicale, Research Unit 448, Créteil, France. This work addresses the question whether CD38, a negative prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL), plays a role in neoplastic B-cell growth and survival. We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand. The interaction triggers an extensive remodeling of the B-CLL membrane, with relocalization of BCR/CD19 to the CD38/CD31 contact areas, and it also increases cell survival and proliferation. A second event is the up-modulation of the survival receptor CD100, restricted to proliferating cells, and a concomitant decrease of CD72 (low-affinity CD100 ligand and negative regulator of immune responses). The most efficient signals are delivered through sequential interactions between CD38/CD31 and CD100/plexin-B1 (high-affinity CD100 ligand), as inferred by coculture experiments using specific transfectants and blocking monoclonal antibodies (mAbs). The finding that nurselike cells from B-CLL patients express CD31 and plexin-B1, which deliver growth and survival signals to CD38+/CD100+ B-CLL cells, further confirms the model proposed. These findings show that a set of normal receptors and ligands ruling physiologic signaling pathways in B lymphocytes becomes detrimental when expressed in the context of B-CLL cells, ultimately leading to the generation of a tumor reservoir. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A new twist for CD38 antigen expression in CLL John C. Byrd Blood 2005 105: 3002. [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. Aydin Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology Physiol Rev, July 1, 2008; 88(3): 841 - 886. [Abstract] [Full Text] [PDF] S. Aydin, D. Rossi, L. Bergui, G. D'Arena, E. Ferrero, L. Bonello, P. Omede, D. Novero, F. Morabito, A. Carbone, et al. CD38 gene polymorphism and chronic lymphocytic leukemia: a role in transformation to Richter syndrome? Blood, June 15, 2008; 111(12): 5646 - 5653. [Abstract] [Full Text] [PDF] P. E. M. Patten, A. G. S. Buggins, J. Richards, A. Wotherspoon, J. Salisbury, G. J. Mufti, T. J. Hamblin, and S. Devereux CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment Blood, May 15, 2008; 111(10): 5173 - 5181. [Abstract] [Full Text] [PDF] G. Cutrona, M. Colombo, S. Matis, M. Fabbi, M. Spriano, V. Callea, E. Vigna, M. Gentile, S. Zupo, N. Chiorazzi, et al. Clonal heterogeneity in chronic lymphocytic leukemia cells: superior response to surface IgM cross-linking in CD38, ZAP-70-positive cells Haematologica, March 1, 2008; 93(3): 413 - 422. [Abstract] [Full Text] [PDF] S. G. Agrawal, F.-T. Liu, C. Wiseman, S. Shirali, H. Liu, D. Lillington, M.-Q. Du, D. Syndercombe-Court, A. C. Newland, J. G. Gribben, et al. Increased proteasomal degradation of Bax is a common feature of poor prognosis chronic lymphocytic leukemia Blood, March 1, 2008; 111(5): 2790 - 2796. [Abstract] [Full Text] [PDF] S. Deaglio, T. Vaisitti, S. Aydin, L. Bergui, G. D'Arena, L. Bonello, P. Omede, M. Scatolini, O. Jaksic, G. Chiorino, et al. CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential Blood, December 1, 2007; 110(12): 4012 - 4021. [Abstract] [Full Text] [PDF] E. Backman, A.-C. Bergh, I. Lagerdahl, B. Rydberg, C. Sundstrom, G. Tobin, R. Rosenquist, M. Linderholm, and A. Rosen Thioredoxin, produced by stromal cells retrieved from the lymph node microenvironment, rescues chronic lymphocytic leukemia cells from apoptosis in vitro Haematologica, November 1, 2007; 92(11): 1495 - 1504. [Abstract] [Full Text] [PDF] A. Burkle, M. Niedermeier, A. Schmitt-Graff, W. G. Wierda, M. J. Keating, and J. A. Burger Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B-cell chronic lymphocytic leukemia Blood, November 1, 2007; 110(9): 3316 - 3325. [Abstract] [Full Text] [PDF] R. N. Damle, S. Temburni, C. Calissano, S. Yancopoulos, T. Banapour, C. Sison, S. L. Allen, K. R. Rai, and N. Chiorazzi CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells Blood, November 1, 2007; 110(9): 3352 - 3359. [Abstract] [Full Text] [PDF] S. Willimott, M. Baou, S. Huf, S. Deaglio, and S. D. Wagner Regulation of CD38 in proliferating chronic lymphocytic leukemia cells stimulated with CD154 and interleukin-4 Haematologica, October 1, 2007; 92(10): 1359 - 1366. [Abstract] [Full Text] [PDF] J. Durig, P. Ebeling, F. Grabellus, U. R. Sorg, M. Mollmann, P. Schutt, J. Gothert, L. Sellmann, S. Seeber, M. Flasshove, et al. A Novel Nonobese Diabetic/Severe Combined Immunodeficient Xenograft Model for Chronic Lymphocytic Leukemia Reflects Important Clinical Characteristics of the Disease Cancer Res., September 15, 2007; 67(18): 8653 - 8661. [Abstract] [Full Text] [PDF] A. D. Joshi, G. V. Hegde, J. D. Dickinson, A. K. Mittal, J. C. Lynch, J. D. Eudy, J. O. Armitage, P. J. Bierman, R. G. Bociek, M. P. Devetten, et al. ATM, CTLA4, MNDA, and HEM1 in High versus Low CD38 Expressing B-Cell Chronic Lymphocytic Leukemia Clin. Cancer Res., September 15, 2007; 13(18): 5295 - 5304. [Abstract] [Full Text] [PDF] S. Deaglio, T. Vaisitti, R. Billington, L. Bergui, P. Omede', A. A. Genazzani, and F. Malavasi CD38/CD19: a lipid raft-dependent signaling complex in human B cells Blood, June 15, 2007; 109(12): 5390 - 5398. [Abstract] [Full Text] [PDF] T. D. Shanafelt, J. C. Byrd, T. G. Call, C. S. Zent, and N. E. Kay Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia. Ann Intern Med, September 19, 2006; 145(6): 435 - 447. [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. Moreno-Garcia, S. Partida-Sanchez, M. Makris, N. J. Oppenheimer, L. Santos-Argumedo, and F. Schuber CD38 induces apoptosis of a murine pro-B leukemic cell line by a tyrosine kinase-dependent but ADP-ribosyl cyclase- and NAD glycohydrolase-independent mechanism Int. Immunol., July 1, 2006; 18(7): 1029 - 1042. [Abstract] [Full Text] [PDF] L. Frasca, G. Fedele, S. Deaglio, C. Capuano, R. Palazzo, T. Vaisitti, F. Malavasi, and C. M. Ausiello CD38 orchestrates migration, survival, and Th1 immune response of human mature dendritic cells Blood, March 15, 2006; 107(6): 2392 - 2399. [Abstract] [Full Text] [PDF] F. Malavasi Old and new drugs join forces against hematologic malignancies Blood, September 1, 2005; 106(5): 1513 - 1514. [Full Text] [PDF] M. Burger, T. Hartmann, M. Krome, J. Rawluk, H. Tamamura, N. Fujii, T. J. Kipps, and J. A. Burger Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells Blood, September 1, 2005; 106(5): 1824 - 1830. [Abstract] [Full Text] [PDF] M. Nishio, T. Endo, N. Tsukada, J. Ohata, S. Kitada, J. C. Reed, N. J. Zvaifler, and T. J. Kipps Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1{alpha} Blood, August 1, 2005; 106(3): 1012 - 1020. [Abstract] [Full Text] [PDF]

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