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

被引:114
作者
Deaglio, Silvia
Vaisitti, Tiziana
Aydin, Semra
Ferrero, Enza
Malavasi, Fabio
机构
[1] Univ Turin, Sch Med, Dept Genet Biol & Biochem, Lab Immunogenet,Lymphocyte Signalling Unit, I-10126 Turin, Italy
[2] Univ Turin, Sch Med, CeRMS, I-10126 Turin, Italy
关键词
D O I
10.1182/blood-2006-01-013003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The absence of mutations in the IgV genes, together with the presence of ZAP-70 and CD38, are the most reliable negative prognostic markers for chronic lymphocytic leukemia (CLL) patients. Several lines of evidence indicate that CD38 may be not only a diagnostic marker but also a key element in the pathogenetic network in CLL. First, CD38 is a receptor that induces proliferation and increases survival of CLL cells. Second, CD38 signals start upon interaction with the CD31 ligand expressed by stromal and nurselike cells. Third, CD38/CD31 contacts upregulate CD100, a semaphorin involved in sustaining CLL growth. Fourth, evidence that nurselike cells express high levels of CD31 and plexin-Bl, the high-affinity ligand for CD100, offers indirect confirmation for this model of receptor cross-talk. Elements of variation in the clinical course of CD38(+) CLL patients include (1) potential intersection with ZAP-70, a kinase involved in the CD38 signaling pathway in T and natural killer (NK) cells, and (2) the effects of genetic polymorphisms of the receptors involved, at least of CD38 and CD31. Consequently, CD38 together with ZAP-70 appear to be the key elements of a coreceptor pathway that may sustain the signals mediated by the B-cell receptor and potentially by chemokines and their receptors. This would result in acquisition of increased survival potential, providing clues to the poorer prognosis of CD38(+) patients.
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页码:1135 / 1144
页数:10
相关论文
共 124 条
[91]   CD38 signaling in T cells is initiated within a subset of membrane rafts containing Lck and the CD3-ζ subunit of the T cell antigen receptor [J].
Muñoz, P ;
Navarro, MD ;
Pavón, EJ ;
Salmerón, J ;
Malavasi, F ;
Sancho, J ;
Zubiaur, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (50) :50791-50802
[92]   Identification of the enzymatic active site of CD38 by site-directed mutagenesis [J].
Munshi, C ;
Aarhus, R ;
Graeff, R ;
Walseth, TF ;
Levitt, D ;
Lee, HC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (28) :21566-21571
[93]   ZAP-70 is expressed by a subset of normal human B-lymphocytes displaying an activated phenotype [J].
Nolz, JC ;
Tschumper, RC ;
Pittner, BT ;
Darce, JR ;
Kay, NE ;
Jelinek, DF .
LEUKEMIA, 2005, 19 (06) :1018-1024
[94]   CD157, the Janus of CD38 but with a unique personality [J].
Ortolan, E ;
Vacca, P ;
Capobianco, A ;
Armando, E ;
Crivellin, F ;
Horenstein, A ;
Malavasi, F .
CELL BIOCHEMISTRY AND FUNCTION, 2002, 20 (04) :309-322
[95]  
Ottaggio L, 2003, HAEMATOLOGICA, V88, P769
[96]   Cutting edge: T cell migration regulated by CXCR4 chemokine receptor signaling to ZAP-70 tyrosine kinase [J].
Ottoson, NC ;
Pribila, JT ;
Chan, ASH ;
Shimizu, Y .
JOURNAL OF IMMUNOLOGY, 2001, 167 (04) :1857-1861
[97]   Chemotaxis and calcium responses of phagocytes to formyl peptide receptor ligands is differentially regulated by cyclic ADP ribose [J].
Partida-Sánchez, S ;
Iribarren, P ;
Moreno-García, ME ;
Gao, XL ;
Murphy, PM ;
Oppenheimer, N ;
Wang, JM ;
Lund, FE .
JOURNAL OF IMMUNOLOGY, 2004, 172 (03) :1896-1906
[98]   ANALYSIS OF SOMATIC MUTATION IN 5 B-CELL SUBSETS OF HUMAN TONSIL [J].
PASCUAL, V ;
LIU, YJ ;
MAGALSKI, A ;
DEBOUTEILLER, O ;
BANCHEREAU, J ;
CAPRA, JD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (01) :329-339
[99]  
Peacock JW, 1999, J IMMUNOL, V162, P215
[100]   CD38 expression levels in chronic lymphocytic leukemia B cells are associated with activation marker expression and differential responses to interferon stimulation [J].
Pittner, BT ;
Shanafelt, TD ;
Kay, NE ;
Jelinek, DF .
LEUKEMIA, 2005, 19 (12) :2264-2272