Del Principe Maria Ilaria, Del Poeta Giovanni, Buccisano Francesco, Maurillo Luca, Venditti Adriano, Zucchetto Antonella, Marini Rita, Niscola Pasquale, Consalvo Maria Antonietta Irno, 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
Cattedra di Ematologia, Università Tor Vergata, Ospedale S Eugenio, Via Fiume Giallo, 430 MA, 00144 Roma, Rome, Italy.
Blood. 2006 Aug 1;108(3):853-61. doi: 10.1182/blood-2005-12-4986. Epub 2006 Apr 6.
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.
B 细胞慢性淋巴细胞白血病（B-CLL）的临床病程具有多样性，需要在临床分期系统中加入新的生物学参数，以预测疾病进展缓慢或迅速。我们对289例B-CLL患者的70-kDa ζ相关蛋白（ZAP-70）、CD38、可溶性CD23（sCD23）和细胞遗传学进行了研究。ZAP-70阳性（P < 0.001）、CD38阳性（P < 0.001）和sCD23阳性患者（分别为P < 0.001和P = 0.013）的无进展生存期（PFS）和总生存期（OS）均较短。与ZAP-70阴性/CD38阴性或IgV(H)基因发生突变的ZAP-70阴性患者相比，ZAP-70阳性/CD38阳性或IgV(H)状态未发生突变的ZAP-70阳性患者的PFS（P < 0.001）和OS（分别为P < 0.001和P < 0.001）均较短。不一致的患者表现出中间转归。注意，即使CD38阴性或发生突变，ZAP-70阳性患者的PFS也较短；而即使CD38阳性或未发生突变，ZAP-70阴性患者的PFS也较长。此外，在正常核型组（P < 0.001）和高危细胞遗传学亚组（P = 0.02）中，ZAP-70阳性均与较短的PFS相关。多因素分析证实了ZAP-70表达的预测价值。因此，通过流式细胞术检测的ZAP-70蛋白提高了细胞遗传学的预后意义，并且似乎比IgV(H)基因突变状态更能准确预测疾病转归。基于此，我们建议并有意开展一项针对ZAP-70阳性患者的早期干预与观察的前瞻性随机试验。
