title: 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.
abstract: 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 nurse-like cells. Third, CD38/CD31 contacts up-regulate CD100, a semaphorin involved in sustaining CLL growth. Fourth, evidence that nurselike cells express high levels of CD31 and plexin-B1, 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.
authors.affiliation: Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vaisitti
authors.forename: Semra
authors.initials: S
authors.lastname: Aydin
authors.forename: Enza
authors.initials: E
authors.lastname: Ferrero
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D018572:Disease-Free Survival; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C093224:CD100 antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019707:Receptors, Chemokine; D039961:Semaphorins; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1