|
|
Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2003-03-0989.
Submitted March 31, 2003
Accepted May 13, 2003
CD38 is a signaling molecule in B-chronic lymphocytic leukemia cells
Silvia Deaglio, Andrea Capobianco, Luciana Bergui, Jan Durig, Fortunato Morabito, Ulrich Duehrsen, and Fabio Malavasi*
Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Turin Medical School, Turin, Italy; Research Center on Experimental Medicine (CERMS), University of Turin Medical School, Turin, Italy
Department of Medicine and Experimental Oncology, University of Turin Medical School, Turin, Italy
Department of Hematology, University Hospital, Essen, Germany
Bone Marrow Transplant Center, Bianchi, Melacrino, Morelli Hospital, Reggio Calabria, Italy
* Corresponding author; email: fabio.malavasi{at}unito.it.
The prognosis for B-chronic lymphocytic leukemia (B-CLL) patients 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 receptorial role with pathogenetic valencies, 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 the CD38 functionality. IL-2 induced a marked up-modulation and surface rearrangement of CD38 in all the patients studied. Upon 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 BCR complex and CD19. Upon mAb binding, CD38 translocates to the membrane lipid microdomains, as shown by a co-localization with the GM1 ganglioside and with CD81, a raft-resident protein. Lastly, CD38 signaling in IL-2-treated B-CLL cells prolongs survival and induces 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:
|
|
|
|
 
C. Calissano, R. N. Damle, G. Hayes, E. J. Murphy, M. K. Hellerstein, C. Moreno, C. Sison, M. S. Kaufman, J. E. Kolitz, S. L. Allen, et al.
In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia
Blood,
November 26, 2009;
114(23):
4832 - 4842.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Zucchetto, D. Benedetti, C. Tripodo, R. Bomben, M. Dal Bo, D. Marconi, F. Bossi, D. Lorenzon, M. Degan, F. M. Rossi, et al.
CD38/CD31, the CCL3 and CCL4 Chemokines, and CD49d/Vascular Cell Adhesion Molecule-1 Are Interchained by Sequential Events Sustaining Chronic Lymphocytic Leukemia Cell Survival
Cancer Res.,
May 1, 2009;
69(9):
4001 - 4009.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Jamroziak, Z. Szemraj, O. Grzybowska-Izydorczyk, J. Szemraj, M. Bieniasz, B. Cebula, K. Giannopoulos, E. Balcerczak, D. Jesionek-Kupnicka, M. Kowal, et al.
CD38 Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians
Cancer Epidemiol. Biomarkers Prev.,
March 1, 2009;
18(3):
945 - 953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. BOELENS, S. LUST, B. VANHOECKE, and F. OFFNER
Chronic Lymphocytic Leukaemia
Anticancer Res,
February 1, 2009;
29(2):
605 - 615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Guarini, S. Chiaretti, S. Tavolaro, R. Maggio, N. Peragine, F. Citarella, M. R. Ricciardi, S. Santangelo, M. Marinelli, M. S. De Propris, et al.
BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells
Blood,
August 1, 2008;
112(3):
782 - 792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
V. Gattei, P. Bulian, M. I. Del Principe, A. Zucchetto, L. Maurillo, F. Buccisano, R. Bomben, M. Dal-Bo, F. Luciano, F. M. Rossi, et al.
Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia
Blood,
January 15, 2008;
111(2):
865 - 873.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
N. Gallay, L. Anani, A. Lopez, P. Colombat, C. Binet, J. Domenech, B. B. Weksler, F. Malavasi, and O. Herault
The Role of Platelet/Endothelial Cell Adhesion Molecule 1 (CD31) and CD38 Antigens in Marrow Microenvironmental Retention of Acute Myelogenous Leukemia Cells
Cancer Res.,
September 15, 2007;
67(18):
8624 - 8632.
[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]
|
|
|
|
|
|
|
C. Ian Mockridge, K. N. Potter, I. Wheatley, L. A. Neville, G. Packham, and F. K. Stevenson
Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status
Blood,
May 15, 2007;
109(10):
4424 - 4431.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Tinhofer, G. Rubenzer, C. Holler, E. Hofstaetter, M. Stoecher, A. Egle, M. Steurer, and R. Greil
Expression levels of CD38 in T cells predict course of disease in male patients with B-chronic lymphocytic leukemia
Blood,
November 1, 2006;
108(9):
2950 - 2956.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Liu, I. A. Kriksunov, R. Graeff, C. Munshi, H. C. Lee, and Q. Hao
Structural Basis for the Mechanistic Understanding of Human CD38-controlled Multiple Catalysis
J. Biol. Chem.,
October 27, 2006;
281(43):
32861 - 32869.
[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. 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]
|
|
|
|
|
|
|
I. Hus, M. Podhorecka, A. Bojarska-Junak, J. Rolinski, M. Schmitt, M. Sieklucka, E. Wasik-Szczepanek, and A. Dmoszynska
The clinical significance of ZAP-70 and CD38 expression in B-cell chronic lymphocytic leukaemia
Ann. Onc.,
April 1, 2006;
17(4):
683 - 690.
[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]
|
|
|
|
|
|
|
O. Tliba, J. A. Cidlowski, and Y. 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. Pharmacol.,
August 1, 2004;
66(2):
322 - 329.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Jaksic, M. M. Kardum Paro, I. Kardum Skelin, R. Kusec, V. Pejsa, and B. Jaksic
CD38 on B-cell chronic lymphocytic leukemia cells has higher expression in lymph nodes than in peripheral blood or bone marrow
Blood,
March 1, 2004;
103(5):
1968 - 1969.
[Full Text]
[PDF]
|
|
|
|
|
