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 IgVH 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 IgVH 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.
| Original language | English |
|---|---|
| Pages (from-to) | 853-861 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 108 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Aug 1 2006 |
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ASJC Scopus subject areas
- Hematology
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Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. / Del Principe, Maria Ilaria; Del Poeta, Giovanni; Buccisano, Francesco; Maurillo, Luca; Venditti, Adriano; Zucchetto, Antonella; Marini, Rita; Niscola, Pasquale; Irno Consalvo, Maria Antonietta; Mazzone, Carla; Ottaviani, Licia; Panetta, Paola; Bruno, Antonio; Bomben, Riccardo; Suppo, Giovanna; Degan, Massimo; Gattei, Valter; De Fabritiis, Paolo; Cantonetti, Maria; Lo Coco, Francesco; Del Principe, Domenico; Amadori, Sergio.
In: Blood, Vol. 108, No. 3, 01.08.2006, p. 853-861.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia
AU - Del Principe, Maria Ilaria
AU - Del Poeta, Giovanni
AU - Buccisano, Francesco
AU - Maurillo, Luca
AU - Venditti, Adriano
AU - Zucchetto, Antonella
AU - Marini, Rita
AU - Niscola, Pasquale
AU - Irno Consalvo, Maria Antonietta
AU - Mazzone, Carla
AU - Ottaviani, Licia
AU - Panetta, Paola
AU - Bruno, Antonio
AU - Bomben, Riccardo
AU - Suppo, Giovanna
AU - Degan, Massimo
AU - Gattei, Valter
AU - De Fabritiis, Paolo
AU - Cantonetti, Maria
AU - Lo Coco, Francesco
AU - Del Principe, Domenico
AU - Amadori, Sergio
PY - 2006/8/1
Y1 - 2006/8/1
N2 - 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 IgVH 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 IgVH 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.
AB - 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 IgVH 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 IgVH 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.
UR - http://www.scopus.com/inward/record.url?scp=33746589459&partnerID=8YFLogxK
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U2 - 10.1182/blood-2005-12-4986
DO - 10.1182/blood-2005-12-4986
M3 - Article
C2 - 16601244
AN - SCOPUS:33746589459
VL - 108
SP - 853
EP - 861
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -