title: Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia.
abstract: The clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is variable, and novel biologic parameters need to be added to the clinical staging systems to predict an indolent or aggressive outcome. We investigated the 70-kDa zeta-associated protein (ZAP-70), CD38, soluble CD23 (sCD23), and cytogenetics in 289 patients with B-CLL. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70(+) (P < .001), in CD38(+) (P < .001) and in sCD23(+) patients (P < .001 and P = .013, respectively). ZAP-70(+)CD38(+) or ZAP-70(+) patients with an unmutated IgV(H) status showed both a shorter PFS (P < .001) and OS (P < .001 and P < .001, respectively) as compared with ZAP-70(-)/CD38(-) or ZAP-70(-) patients with mutated IgV(H) genes. Discordant patients showed an intermediate outcome. Note, ZAP-70(+) patients even if CD38(-) or mutated showed a shorter PFS, whereas ZAP-70(-) patients even if CD38(+) or unmutated had a longer PFS. Furthermore, ZAP-70 positivity was associated with a shorter PFS both within normal karyotype (P < .001) and within the poor-risk cytogenetic subset (P = .02). The predictive value of ZAP-70 expression was confirmed in multivariate analysis. Thus, ZAP-70 protein determined by flow cytometry improves the prognostic significance of cytogenetics and appears to be a better predictor of outcomes than IgV(H) gene mutational status. On this line, we recommend and are also interested in conducting a prospective randomized trial of early intervention versus observation for ZAP-70(+) patients.
authors.affiliation: Cattedra di Ematologia, Università Tor Vergata, Ospedale S Eugenio, Via Fiume Giallo, 430 MA, 00144 Roma, Rome, Italy.
authors.forename: Maria Ilaria
authors.initials: MI
authors.lastname: Del Principe
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.forename: Luca
authors.initials: L
authors.lastname: Maurillo
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.forename: Antonella
authors.initials: A
authors.lastname: Zucchetto
authors.forename: Rita
authors.initials: R
authors.lastname: Marini
authors.forename: Pasquale
authors.initials: P
authors.lastname: Niscola
authors.forename: Maria Antonietta Irno
authors.initials: MA
authors.lastname: Consalvo
authors.forename: Carla
authors.initials: C
authors.lastname: Mazzone
authors.forename: Licia
authors.initials: L
authors.lastname: Ottaviani
authors.forename: Paola
authors.initials: P
authors.lastname: Panetta
authors.forename: Antonio
authors.initials: A
authors.lastname: Bruno
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bomben
authors.forename: Giovanna
authors.initials: G
authors.lastname: Suppo
authors.forename: Massimo
authors.initials: M
authors.lastname: Degan
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Paolo
authors.initials: P
authors.lastname: de Fabritiis
authors.forename: Maria
authors.initials: M
authors.lastname: Cantonetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Coco
authors.forename: Domenico
authors.initials: D
authors.lastname: Del Principe
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020732:Cytogenetic Analysis; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D017455:Receptors, IgE / Q000032:analysis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis* / Q000235:genetics
chemical_list: D007135:Immunoglobulin Variable Region; D017455:Receptors, IgE; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1