B细胞慢性淋巴细胞白血病中ZAP-70蛋白表达与CD38阳性情况

ZAP-70 protein expression and CD38 positivity in B-cell chronic lymphocytic leukemia.

作者信息

Ertault-Daneshpouy Marjan, Noguera Maria Elena, Gisselbrecht Christian, Haddad Albert, Brice Pauline, Marolleau Jean-Pierre, Soulier Jean, Mounier Nicolas

机构信息

Institut Universitaire d'Hématologie, Hopital St Louis, 75010 Paris, France.

出版信息

Clin Adv Hematol Oncol. 2008 Jan;6(1):55-63.

PMID:18322442

Abstract

BACKGROUND

The clinical course, disease progression, and survival of B-cell chronic lymphocytic leukemia (B-CLL) have been correlated with immunoglobulin heavy-chain variable region mutation status. The biologic parameters 70-kDa zeta-associated protein (ZAP-70) and CD38 expression are easier and faster surrogate markers for mutational status.

OBJECTIVE

To assess retrospectively ZAP-70 expression in B-CLL cells using flow cytometry and examine its relationship with CD38 expression and the median time from diagnosis to initial therapy.

METHODS

Ninety-four unselected patients who had their follow-up in the outpatient clinic from 2004 to 2005 were reviewed for immunophenotyping ZAP-70 and CD38 expression. Direct immunolabeling with clone 2E3.2, isotype IgG2a, enabled easy quantification of ZAP-70 by flow cytometry in association with CD38 expression; in addition, the mean fluorescence intensity ratio (MFIR) of CD19+CD5+ B-CLL cells compared to an isotype control monoclonal antibody was determined.

RESULTS

ZAP-70 expression levels in B-CLL cells varied widely (0.3-99%). The median time to therapy was significantly shorter for the 54 patients with 20% or more ZAP-70+ cells (30 months) than for the 40 patients with less than 20% ZAP-70+ cells (median time to treatment not reached). The optimal MFIR for classifying patients as ZAP-70+ was 2. Thirty-two patients had a threshold of ZAP-70+CD38+ greater than 30%, with a median time from diagnosis to treatment of 19 months. Regardless of CD38 expression level, CD38 and ZAP-70 expressions were significantly associated. The median interval from diagnosis to initial therapy was 16.2 months for ZAP-70+CD38+ patients, 60 months for ZAP-70+CD38- or ZAP-70-CD38+ patients, and had not yet been reached for ZAP-70-CD38- patients.

CONCLUSION

The association of ZAP-70+CD19+CD5+ B-CLL cells and percentage of CD38+CD19+CD5+ B-CLL cells evaluated by flow cytometry provide reliable methods that could be introduced into a routine diagnostic B-CLL panel to predict outcome.

摘要

背景

B 细胞慢性淋巴细胞白血病（B-CLL）的临床病程、疾病进展及生存期与免疫球蛋白重链可变区突变状态相关。生物学参数 70-kDa ζ 相关蛋白（ZAP-70）和 CD38 表达是更简便快捷的突变状态替代标志物。

目的

采用流式细胞术回顾性评估 B-CLL 细胞中 ZAP-70 的表达，并探讨其与 CD38 表达及从诊断到初始治疗的中位时间的关系。

方法

回顾性分析 2004 年至 2005 年在门诊接受随访的 94 例未经选择的患者，对其进行 ZAP-70 和 CD38 表达的免疫表型分析。使用克隆 2E3.2（同型 IgG2a）进行直接免疫标记，通过流式细胞术可轻松定量 ZAP-70 并同时检测 CD38 表达；此外，还测定了 CD19+CD5+ B-CLL 细胞与同型对照单克隆抗体相比的平均荧光强度比值（MFIR）。

结果

B-CLL 细胞中 ZAP-70 的表达水平差异很大（0.3% - 99%）。ZAP-70+细胞占 20%或更多的 54 例患者从诊断到治疗的中位时间（30 个月）显著短于 ZAP-70+细胞占比小于 20%的 40 例患者（未达到治疗中位时间）。将患者分类为 ZAP-70+的最佳 MFIR 为 2。32 例患者的 ZAP-70+CD38+阈值大于 30%，从诊断到治疗的中位时间为 19 个月。无论 CD38 表达水平如何，CD38 和 ZAP-70 的表达均显著相关。ZAP-70+CD38+患者从诊断到初始治疗的中位间隔时间为 16.2 个月，ZAP-70+CD38-或 ZAP-70-CD38+患者为 60 个月，ZAP-70-CD38-患者尚未达到。