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
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
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DOI：
10.1002/cyto.b.20483
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发表时间：
2009-11-01
影响因子：
3.4
通讯作者：
Haferlach, Torsten
中科院分区：
文献类型：
--
作者：
Kern, Wolfgang;Dicker, Frank;Haferlach, Torsten
背景资料：ZAP-70在慢性淋巴细胞白血病（CLL）中提供了重要的预后信息;然而，最合适的抗体克隆和分析方法尚未确定。方法：我们使用SBZAP克隆通过应用三种不同的分析方法测定了1，229例CLL患者中ZAP-70的表达（阳性B细胞%，B细胞中的平均荧光强度（MFI），T细胞：B细胞的MFI比率）。对于所有三种分析方法，ZAP-70表达与IgVH基因的体细胞高突变状态相关（各自P < 0.0001）。最强的相关性被发现为MFI比率（r =-0.475，P < 0.0001）;具有突变和未突变IgVH状态的病例的平均MFI比率显著不同（6.33 vs. 3.34，P < 0.0001）。ZAP-70在单一del（13 q）中表达较弱（5.44 vs.4.44，P = 0.001），而在del（11 q）（3.31 vs.5.29，P < 0.0001）和del（6 q）（3.29 vs.5.18，P = 0.005）中表达较强。在221例可评价病例中，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比率（P = 0.043，RR = 0.64）和CD 38（P = 0.047，RR = 1.20每10%）作为唯一的参数独立相关的时间therapeutic.Conclusions：ZAP-70的表达，使用SBZAP和应用MFI比率T细胞：B细胞的结果在显着关系IgVH突变状态，细胞遗传学和结果，并应进一步分析和考虑在CLL的常规应用。(C)2009年临床细胞计数学会
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. (C) 2009 Clinical Cytometry Society