ZAP-70阳性和ZAP-70阴性B细胞慢性淋巴细胞白血病患者的外周血淋巴细胞表型

Peripheral blood lymphocyte phenotype of ZAP-70⁺ and ZAP-70⁻ patients with B-cell chronic lymphocytic leukaemia.

作者信息

Rivkina A, Holodnuka-Kholodyuk I, Murovska M, Soloveichika M, Lejniece S

机构信息

Riga Stradins University, Internal Diseases Department, Riga LV1007, Latvia.

Riga Stradins University, A. Kirchenstein Institute of Microbiology and Virology, Riga LV1067, Latvia.

出版信息

Exp Oncol. 2015 Mar;37(1):73-6.

PMID:25804237

Abstract

BACKGROUND

Up to now, the immune status of chronic lymphocytic leukemia (CLL) patients in association with the expression of zeta-chain-associated protein kinase 70 (ZAP-70) in leukemic cells has not been evaluated.

AIM

The aim of this work was the study of the peripheral blood (PB) T-lymphocyte phenotypes in ZAP-70-positive (ZAP-70(+)) and ZAP-70-negative (ZAP-70(-)) untreated patients with CLL.

MATERIALS AND METHODS

ZAP-70-, CD25-, CD3-, CD4-, and CD8-positive lymphocytes were enumerated by flow cytometry in PB of 120 untreated CLL patients. CD8+, CD3+CD4+ and CD3+CD25+ cells were counted for the non-leukemic lymphocytes.

RESULTS

The patients were distributed into two groups: the ZAP-70(+) group of high CLL progression (n = 61), and the ZAP-70(-) group of low CLL progression (n = 59). In the ZAP-70(+) group, the ratio CD4/CD8 (0.33 ± 0.62; p = 0.001) and the numbers of the CD3+ (34.8 ± 8.1%; p = 0.01), CD3+CD4+ (24.4% ± 4.8; p = 0.001), and CD3+CD25+ (6.2 ± 0.91%; p = 0.001) lymphocytes were reduced and the percentage of the CD8+ cells (73.1 ± 4.6%; p = 0.0001) was above the norm. In the ZAP-70(-) group, the number of the CD3+CD4+ cells (36.9 ± 6.1%; p = 0.001) was within the norm, but the numbers of the CD8+ (11.3 ± 1.1%; p = 0.0001) and CD3+ (41.2 ± 5.3%; p = 0.05) lymphocytes were reduced; the ratio CD4/CD8 (3.26 ± 0.88; p = 0.001) and the percentage of the CD3+CD25+ cells (27.1 ± 3.4%; p = 0.0001) were above the norm.

CONCLUSIONS

Our data show that the increased CD4/CD8 ratio, caused by the reduced number of the CD8+ lymphocytes, and the increased number of CD3+CD25+ cells are characteristic for the ZAP-70(-) group (slow progressing) of untreated CLL patients. In ZAP-70(+) patients, the CD4/CD8 ratio was significantly below the norm indicating an active disease process. Results of our study contribute to identification of CLL patients with different prognosis in routine diagnostic/prognostic procedures.

摘要

背景

迄今为止，尚未评估慢性淋巴细胞白血病（CLL）患者的免疫状态与白血病细胞中ζ链相关蛋白激酶70（ZAP-70）表达之间的关系。

目的

本研究旨在探讨未经治疗的ZAP-70阳性（ZAP-70(+)）和ZAP-70阴性（ZAP-70(-)）CLL患者外周血（PB）T淋巴细胞表型。

材料与方法

采用流式细胞术对120例未经治疗的CLL患者外周血中ZAP-70、CD25、CD3、CD4和CD8阳性淋巴细胞进行计数。对非白血病淋巴细胞计数CD8+、CD3+CD4+和CD3+CD25+细胞。

结果

患者分为两组：CLL进展较快的ZAP-70(+)组（n = 61）和CLL进展较慢的ZAP-70(-)组（n = 59）。在ZAP-70(+)组中，CD4/CD8比值（0.33±0.62；p = 0.001）以及CD3+（34.8±8.1%；p = 0.01）、CD3+CD4+（24.4%±4.8；p = 0.001）和CD3+CD25+（6.2±0.91%；p = 0.001）淋巴细胞数量减少，CD8+细胞百分比（73.1±4.6%；p = 0.0001）高于正常水平。在ZAP-70(-)组中，CD3+CD4+细胞数量（36.9±6.1%；p = 0.001）在正常范围内，但CD8+（11.3±1.1%；p = 0.0001）和CD3+（41.2±5.3%；p = 0.05）淋巴细胞数量减少；CD4/CD8比值（3.26±0.88；p = 0.001）和CD3+CD25+细胞百分比（27.1±3.4%；p = 0.0001）高于正常水平。

结论

我们的数据表明，CD8+淋巴细胞数量减少导致CD4/CD8比值升高以及CD3+CD25+细胞数量增加是未经治疗的CLL患者ZAP-70(-)组（进展缓慢）的特征。在ZAP-70(+)患者中，CD4/CD8比值显著低于正常水平，表明疾病进程活跃。我们的研究结果有助于在常规诊断/预后程序中识别具有不同预后的CLL患者。