Del Giudice Ilaria, Morilla Alison, Osuji Nnenna, Matutes Estella, Morilla Ricardo, Burford Anna, Maravelaki Sonia, Owusu-Ankomah Kwasi, Swansbury John, A'Hern Roger, Brito-Babapulle Vasantha, Catovsky Daniel
Section of Hemato-Oncology, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Cancer. 2005 Nov 15;104(10):2124-32. doi: 10.1002/cncr.21437.
Zeta-chain associated protein (ZAP)-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region (IgVH) mutation in chronic lymphocytic leukemia (CLL), but it is still not clear whether it is an independent prognostic factor.
The authors evaluated ZAP-70 expression by flow cytometry in 201 untreated patients and correlated ZAP-70 levels with CD38 expression, genetic abnormalities detected by fluorescence in situ hybridization (FISH), and the time from diagnosis to first treatment.
Fifty-seven patients (28%) were positive for ZAP-70 (> or = 20%). Positive ZAP-70 status was associated with advanced disease stage, atypical morphology, CD38-positive status, trisomy 12, del(6q), or no detectable abnormalities; negative ZAP-70 status was correlated with del(13q) as a sole abnormality. The treatment-free interval (TFI) was 17.7 months for ZAP-70-positive patients and 44.6 months for ZAP-70-negative patients (P < 0.001). Multivariate analysis in 117 patients identified advanced stage, CD38 > or = 7%, and the absence of del(13q) as a sole abnormality as independent factors for short TFI. Excluding FISH, ZAP-70 status acquired independent prognostic value along with CD38 status. The authors proposed a risk model that combines ZAP-70 and CD38 to identify patients who are likely to progress. When both markers were positive, the TFI was 12 months; when both were negative, the median TFI was 54 months; a median TFI of 26 months was observed in patients who had discordant results (P < 0.00001).
The current findings suggested that both ZAP-70 and CD38 should be tested prospectively in all patients with early-stage CLL.
ζ链相关蛋白（ZAP）-70已被提议作为慢性淋巴细胞白血病（CLL）中免疫球蛋白重链可变区（IgVH）突变的替代标志物，但它是否为独立的预后因素仍不明确。
作者通过流式细胞术评估了201例未经治疗患者的ZAP-70表达，并将ZAP-70水平与CD38表达、荧光原位杂交（FISH）检测到的基因异常以及从诊断到首次治疗的时间进行关联分析。
57例患者（28%）ZAP-70呈阳性（≥20%）。ZAP-70阳性状态与疾病晚期、非典型形态、CD38阳性状态、12号染色体三体、6号染色体长臂缺失（del(6q)）或无可检测到的异常相关；ZAP-70阴性状态与仅存在13号染色体长臂缺失（del(13q)）相关。ZAP-70阳性患者的无治疗间期（TFI）为17.7个月，ZAP-70阴性患者为44.6个月（P<0.001）。对117例患者进行多因素分析，确定疾病晚期、CD38≥7%以及不存在仅为13号染色体长臂缺失这一异常为TFI短的独立因素。排除FISH因素后，ZAP-70状态与CD38状态一起获得了独立的预后价值。作者提出了一个结合ZAP-7０和CD38的风险模型，以识别可能进展的患者。当两个标志物均为阳性时，TFI为12个月；当两者均为阴性时，中位TFI为54个月；结果不一致的患者中位TFI为26个月（P<0.00001）。
目前的研究结果表明，所有早期CLL患者均应前瞻性检测ZAP-70和CD38。
