使用SBZAP抗体通过流式细胞术测定ZAP-70表达与1229例慢性淋巴细胞白血病患者的IgVH突变状态及细胞遗传学的相关性。

Correlation of flow cytometrically determined expression of ZAP-70 using the SBZAP antibody with IgVH mutation status and cytogenetics in 1,229 patients with chronic lymphocytic leukemia.

作者信息

Kern Wolfgang, Dicker Frank, Schnittger Susanne, Haferlach Claudia, Haferlach Torsten

机构信息

MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, Munich 81377, Germany.

出版信息

Cytometry B Clin Cytom. 2009 Nov;76(6):385-93. doi: 10.1002/cyto.b.20483.

DOI:10.1002/cyto.b.20483

PMID:19479984

Abstract

BACKGROUND

ZAP-70 provides an important prognostic information in chronic lymphocytic leukemia (CLL); however, the most appropriate antibody clone and way of analysis have not yet been defined.

METHODS

We determined ZAP-70 expression in 1,229 patients with CLL using the SBZAP clone by applying three different ways of analysis (% positive B-cells, mean fluorescence intensity (MFI) in B-cells, MFI ratio T-cells:B-cells).

RESULTS

ZAP-70 expression was related to somatic hypermutation status of IgVH genes for all three ways of analysis (P < 0.0001 each). The strongest correlation was found for MFI ratio (r = -0.475, P < 0.0001); cases with mutated and unmutated IgVH status significantly differed in their mean MFI ratio (6.33 vs. 3.34, P < 0.0001). ZAP-70 expression was weaker in sole del(13q) (5.44 vs. 4.44, P = 0.001) and stronger in del(11q) (3.31 vs. 5.29, P < 0.0001) and del(6q) (3.29 vs. 5.18, P = 0.005). MFI ratio was significantly related to time to therapy (P = 0.004, RR = 0.79) in 221 evaluable cases. Multivariate analysis proved MFI ratio (P = 0.043, RR = 0.64) and CD38 (P = 0.047, RR = 1.20 per 10%) as only parameters independently related to time to therapy.

CONCLUSIONS

Determination of ZAP-70 expression using SBZAP and applying MFI ratio T-cells:B-cells results in significant relations to IgVH mutation status, cytogenetics, and outcome and should be further analyzed and considered for routine application in CLL.

摘要

背景

ZAP-70在慢性淋巴细胞白血病（CLL）中提供重要的预后信息；然而，最合适的抗体克隆及分析方法尚未确定。

方法

我们通过应用三种不同的分析方法（阳性B细胞百分比、B细胞中的平均荧光强度（MFI）、T细胞与B细胞的MFI比值），使用SBZAP克隆测定了1229例CLL患者的ZAP-70表达。

结果

对于所有三种分析方法，ZAP-70表达均与IgVH基因的体细胞超突变状态相关（每种方法P < 0.0001）。发现MFI比值的相关性最强（r = -0.475，P < 0.0001）；IgVH状态突变和未突变的病例其平均MFI比值有显著差异（6.33对3.34，P < 0.0001）。ZAP-70表达在单纯del(13q)中较弱（5.44对4.44，P = 0.001），在del(11q)中较强（3.31对5.29，P < 0.0001）以及在del(6q)中较强（3.29对5.18，P = 0.005）。在221例可评估病例中，MFI比值与治疗时间显著相关（P = 0.004，RR = 0.79）。多变量分析证明MFI比值（P = 0.043，RR = 0.64）和CD38（P = 0.047，每10% RR = 1.20）是仅与治疗时间独立相关的参数。