Surface antigen expression in chronic lymphocytic leukemia: clustering analysis, interrelationships and effects of chromosomal abnormalities

Surface antigen expression in chronic lymphocytic leukemia: clustering analysis, interrelationships and effects of chromosomal abnormalities
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DOI:
10.1038/sj.leu.2402363
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发表时间:
2002-02-01
期刊:
影响因子:
11.4
通讯作者:
Vilpo, J
Vilpo, J
中科院分区:
医学1区
文献类型:
--
作者:
Hulkkonen, J;Vilpo, L;Vilpo, J

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慢性淋巴细胞白血病 (CLL) 是 B 淋巴细胞白血病的一种表型可区分的形式。采用流式细胞术对35例经典CLL病例进行表面膜抗原表达模式的规律性、相互关系以及三种常见染色体畸变(即11q缺失、13q缺失和12三体性)的影响。 31个单独抗原的双向聚类分析揭示了三种表达模式:(1)大多数情况下大多数细胞呈阳性(CD5、CD19、CD20、CD23、CD27、CD40、CD45、CD45RA); (2) 大多数情况下大多数细胞呈阴性(CD10、CD14、CD34、CD122、CD154、mlgG); (3) 混合模式,阳性病例数量不同,个体病例中阳性细胞百分比不同(CD11c、CD21、CD22、CD25、CD38、CD45RO、CD79b、CD80、CD95、CD124、CD126、CD130、FMC7、mlgD、mlgkappa、mlglambda、mlgM)。即使抗原属于完全不同的基因家族,几种抗原的表达也具有很强的相互依赖性。这样的抗原对是:CD11c/CD21; CD19/CD45; CD191CD79b; CD22/CD45RA; CD23/lgkappa; CD25/mlgM; CD27/CD45; CD45/CD79b; CD45RA/lgkappa。相反,一些抗原的表达是相互排斥的,最好的例子是CD45RA/CD45RO、CD38/CD80和CD45RA/CD80。染色体臂11q的缺失减弱了剪接变体CD45RA的表达,但增强了CD45RO的表达。相反,12 三体病例与 CD45RA 表达增强和 CD45RO 表达减弱相关。同样,12 三体性与 CD27 和 mlgkappa 表达增强相关。信号表面膜抗原的可变水平、它们的相互作用以及遗传畸变的干扰可能会影响 CLL 的临床进展和药物反应。
Chronic lymphocytic leukemia (CLL) is a phenotypically distinguishable form of B-lymphold leukemias. The regularity of surface membrane antigen expression patterns, their interrelationships as well as the effects of the three frequent chromosomal aberrations, ie 11q deletion, 13q deletion and trisomy 12, were investigated in 35 classic CLL cases by flow cytometry. The two-way cluster analysis of 31 individual antigens revealed three expression patterns: (1) most cells in most cases positive (CD5, CD19, CD20, CD23, CD27, CD40, CD45, CD45RA); (2) most cells in most cases negative (CD10, CD14, CD34, CD122, CD154, mlgG); and (3) a mixed pattern with a variable number of positive cases and a variable percentage of positive cells in individual cases (CD11c, CD21, CD22, CD25, CD38, CD45RO, CD79b, CD80, CD95, CD124, CD126, CD130, FMC7, mlgD, mlgkappa, mlglambda, mlgM). The expressions of several antigens were strongly interdependent, even when antigens belonged to entirely different gene families. Such antigen pairs were: CD11c/CD21; CD19/CD45; CD191CD79b; CD22/CD45RA; CD23/lgkappa; CD25/mlgM; CD27/CD45; CD45/CD79b; CD45RA/lgkappa. In contrast, the expression of some antigens was mutually exclusive, the best examples being CD45RA/CD45RO, CD38/CD80 and CD45RA/CD80. Deletion of chromosome arm 11q attenuated expression of splicing variant CD45RA, but enhanced CD45RO expression. In contrast, cases of trisomy 12 were associated with enhanced CD45RA and attenuated CD45RO expression. Similarly, trisomy 12 was associated with enhanced CD27 and mlgkappa expression. The variable levels of signaling surface membrane antigens, their interactions and interference by genetic aberrations are likely to affect the clinical progression and drug response of CLL.