-
Blood.
2006 Aug 1;108(3):853-61. Epub 2006 Apr 6.
-
Clinical significance of ZAP-70 protein expression
in B-cell chronic lymphocytic leukemia.
Del
Principe MI,
Del Poeta G, Buccisano F, Maurillo L, Venditti A,
Zucchetto A, Marini R, Niscola P, Consalvo MA,
Mazzone C, Ottaviani L, Panetta P, Bruno A, Bomben
R, Suppo G, Degan M, Gattei V, de Fabritiis P,
Cantonetti M, Lo Coco F, Del Principe D, Amadori S.
Cattedra di Ematologia, Universita
Tor Vergata, Ospedale S Eugenio, Via Fiume Giallo,
430 MA, 00144 Roma, Rome, Italy.
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.
PMID: 16601244 [PubMed - indexed for
MEDLINE]