The CD38 ectoenzyme family: advances in basic science and clinical practice.
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. CD38(high) B-CLL cases show activated phenotypic features as compared with CD38(low) cases. Moreover, a greater percentage of Ki-67 and telomerase activity is documented among CD38(high) 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-expressing 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.
Morabito
Fortunato
F
Unità Operativa di Ematologia, Azienda Ospedaliera di Cosenza, Cosenza, Italy. fortunato_morabito@tin.it
Damle
Rajendra N
RN
Deaglio
Silvia
S
Keating
Michael
M
Ferrarini
Manlio
M
Chiorazzi
Nicholas
N
D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D011379:Prognosis
D015703:Antigens, CD; D051997:ADP-ribosyl Cyclase 1