title: Prognostic significance of combined analysis of ZAP-70 and CD38 in chronic lymphocytic leukemia.
abstract: The clinical heterogeneity that characterizes chronic lymphocytic leukemia (CLL) poses critical questions concerning the identification of high risk patients. Unmutated IgV(H) genes, CD38 and ZAP-70 expression have emerged as the most useful tools in identifying aggressive CLL. The simultaneous expression of ZAP-70 and CD38 in 157 patients with CLL has been evaluated. Fifty-seven patients (36%) were positive for ZAP-70 and 46 patients (29%) were positive for CD38. Both molecules were highly correlated and predictive of the clinical course of the disease. According to the simultaneous evaluation of ZAP-70 and CD38, patients were divided into three groups. In 81 patients (52%), there was a negative concordance of both molecules (ZAP-70(-)/CD38(-)); in 27 patients (17%) there was a positive concordance (ZAP-70(+)/CD38(+)); in 49 patients (31%) there was a discordant expression (ZAP-70(+)/CD38(-) and ZAP-70(-)/CD38(+)). A comparison of the clinical and laboratory data showed in ZAP-70(+)/CD38(+) patients a significantly higher bone marrow and peripheral blood lymphocytosis, lower hemoglobin levels, more advanced clinical stage, and higher number of unmutated IgV(H) status with respect to the other two groups. Furthermore, ZAP-70(+)/CD38(+) patients displayed a much shorter treatment-free interval (median 12 months vs 42 months in discordant patients and not reached in ZAP-70(-)CD38(-) patients). These results prove that the concomitant evaluation of ZAP-70 and CD38 expression allows the separation of CLL patients in prognostic subgroups and suggest that their simultaneous assessment should become an integral component of the CLL diagnostic grid.
authors.affiliation: Hematology Oncology Unit, National Cancer Institute, Fondazione G. Pascale, Via Mariano Semmola, Naples, Italy. giovannidarena@libero.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Arena
authors.forename: Michela
authors.initials: M
authors.lastname: Tarnani
authors.forename: Carlo
authors.initials: C
authors.lastname: Rumi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vaisitti
authors.forename: Semra
authors.initials: S
authors.lastname: Aydin
authors.forename: Rosaria
authors.initials: R
authors.lastname: De Filippi
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinto
authors.forename: Patrizia
authors.initials: P
authors.lastname: Chiusolo
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis* / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1