The CD38 Ectoenzyme Family: Advances in Basic Science and Clinical Practice

Fortunato Morabito,Rajendra N Damle,Nicholas Chiorazzi,Manlio Ferrarini,Silvia Deaglio,Michael Keating

doi:10.2119/2006-00110.morabito

Abstract

One aim of this session given at the Torino CD38 Meeting in June, 2006 was to review the role of CD38 in B-cell Chronic Lymphocytic Leukemia (B-CLL), and its potential as a therapeutic target. CD38high B-CLL cases show activated phenotypic features as compared with CD38low cases. Moreover, a greater percentage of Ki-67 and telomerase activity is documented among CD38high cases. Also, CD38 is not merely a negative prognostic marker in B-CLL, but also a key element in the pathogenetic network underlying the disease. A large series of B-CLL cases investigating the CD38 expression on bone marrow B-cells identified CD38 value <10% as the cut-off predicting a longer time to treatment. However, neither CD38 nor ZAP-70 by themselves or in combination were able to anticipate IgVH mutational status. Transferring these findings into clinical ground, 3 groups of B-CLL cases were identified with significantly different clinical courses: i.e., low-risk (no negative prognostic factor), intermediate-risk (1 negative prognostic factor) and high-risk (2–3 negative prognostic factors) patients. Altogether these results suggest that: i) CD38-ex-pressing cells present not only an activation status, but also a different stage differentiation with a more repeated turnover; ii) CD38 contributes to controlling a signaling pathway that confers to B-CLL cells an increased proliferative potential, enhancing aggressiveness of this variant; iii) different CD38 cut off values should be considered for peripheral blood and bone marrow; iv) CD38 seems to independently contribute to prognostic stratification of B-CLL.

Highlights

At many stages of differentiation, B lymphocytes express surface membrane CD38
Several groups have shown that the simultaneous assessment of CD38 and ZAP-70 expression adds to the diagnostic power and offers a better identification of aggressive B-CLL. These findings suggest that CD38 and ZAP-70 may be functionally linked in controlling a signaling pathway that confers to B-CLL cells an increased proliferative potential
Keating pointed out the relationship between CD38 expression and other prognostic factors associated with the patient, with tumor burden (Rai and Binet stages and β 2 microglobulin) and with other biological characteristics of the leukemic B-CLL cell [9]

Summary

Introduction

At many stages of differentiation, B lymphocytes express surface membrane CD38. Activated mature B cells express CD38 and undergo a few rounds of replication before being recruited to sites (germinal centers, GC) within secondary follicles. Clonal B-CLL cells were shown to express Zeta chainassociated protein (ZAP-70), as detected by flow cytometry, irrespective of their CD38 status, especially at higher percentages by those in the bone marrow than by those in circulation. ZAP-70, normally found in T lymphocytes, has been reported recently to be present in normal B cells upon activation and expressed by clonal B-CLL cells.

Results

Conclusion