Hulkkonen J, Vilpo L, Hurme M, Vilpo J
Department of Microbiology and Immunology, University of Tampere Medical School and Laboratory Center of Tampere University Hospital, Tampere, Finland.
Leukemia. 2002 Feb;16(2):178-85. doi: 10.1038/sj.leu.2402363.
Chronic lymphocytic leukemia (CLL) is a phenotypically distinguishable form of B-lymphoid 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, mIgG); 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, mIgD, mIgkappa, mIglambda, mIgM). 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; CD19/CD79b; CD22/CD45RA; CD23/Igkappa; CD25/mIgM; CD27/CD45; CD45/CD79b; CD45RA/Igkappa. 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 mIgkappa 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.
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。通过流式细胞术对35例经典CLL病例的表面膜抗原表达模式的规律性、它们之间的相互关系以及三种常见染色体畸变(即11q缺失、13q缺失和三体12)的影响进行了研究。对31种个体抗原的双向聚类分析揭示了三种表达模式:(1)大多数病例中的大多数细胞呈阳性(CD5、CD19、CD20、CD23、CD27、CD40、CD45、CD45RA);(2)大多数病例中的大多数细胞呈阴性(CD10、CD14、CD34、CD122、CD154、mIgG);(3)一种混合模式,个别病例中阳性病例数量和阳性细胞百分比各不相同(CD11c、CD21、CD22、CD25、CD38、CD45RO、CD79b、CD80、CD95、CD124、CD126、CD130、FMC7、mIgD、mIgκ、mIgλ、mIgM)。即使抗原属于完全不同的基因家族,几种抗原的表达也高度相互依赖。这样的抗原对有:CD11c/CD21;CD19/CD45;CD19/CD79b;CD22/CD45RA;CD23/Igκ;CD25/mIgM;CD27/CD45;CD45/CD79b;CD45RA/Igκ。相反,一些抗原的表达相互排斥,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,三体12的病例与CD45RA表达增强和CD45RO表达减弱有关。同样,三体12与CD27和mIgκ表达增强有关。信号表面膜抗原的可变水平、它们的相互作用以及基因畸变的干扰可能会影响CLL的临床进展和药物反应。