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: Silvia Deaglio, Tiziana Vaisitti, Semra Aydin, Enza Ferrero, Fabio Malavasi
• Journal: Blood (Blood) Vol. 108 Issue 4 Pg. 1135-44 (Aug 15 2006) ISSN: 0006-4971 [Print] United States
• PMID: 16621959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antigens, CD
• Biomarkers, Tumor
• CD100 antigen
• Platelet Endothelial Cell Adhesion Molecule-1
• Receptors, Chemokine
• Semaphorins
• ZAP-70 Protein-Tyrosine Kinase
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (genetics, metabolism)
• Antigens, CD (metabolism)
• B-Lymphocytes (metabolism, pathology)
• Biomarkers, Tumor (genetics, metabolism)
• Cell Proliferation
• Disease-Free Survival
• Humans
• Killer Cells, Natural (metabolism, pathology)
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics, metabolism, pathology)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Polymorphism, Genetic
• Receptors, Chemokine (metabolism)
• Semaphorins (metabolism)
• Signal Transduction (genetics)
• Stromal Cells (metabolism, pathology)
• T-Lymphocytes (metabolism, pathology)
• ZAP-70 Protein-Tyrosine Kinase (metabolism)