Quijano Sandra, López Antonio, Rasillo Ana, Sayagués José María, Barrena Susana, Sánchez Maria Luz, Teodosio Cristina, Giraldo Pilar, Giralt Manuel, Pérez M Carmen, Romero Mercedes, Perdiguer Luis, Orfao Alberto
Servicio General de Citometría, Universidad de Salamanca, Salamanca, Spain.
Cytometry B Clin Cytom. 2008 May;74(3):139-49. doi: 10.1002/cyto.b.20390.
B-cell chronic lymphocytic leukemia (B-CLL) is a well-defined clinical entity with heterogeneous molecular and cytogenetic features. Here, we analyze the impact of trisomy 12, del(13q), del(17p), and del(11q) as determined by interphase fluorescence in situ hybridization analysis of purified neoplastic B-CLL cells on their immunophenotype, DNA ploidy status and proliferative rate.Overall, 111 of 180 (62%) B-CLL cases studied displayed one (50%) or more (12%) genetic abnormalities, del(13q) (35%) being more frequently detected than trisomy 12 (23%) followed by del(11q) (9%) and del(17p) (8%). Trisomy 12 was associated with a higher frequency of DNA aneuploidy, stronger expression of CD19, CD20, CD22, CD24, CD27, CD79b, CD38, and sIg and lower reactivity for CD43 with respect to cytogenetically nonaltered cases. In turn, cases with del(13q) displayed greater reactivity for CD20, FMC7, CD27, CD22, CD5, and bcl2, while del(11q) was associated with brighter expression of CD38, FMC7, CD25, and sIg. Hierarchical clustering analysis of the immunophenotype of B-CLL cases with cytogenetic abnormalities allowed the identification of three different groups of patients with increasing frequencies of trisomy 12, del(11q), and del(13q). Remarkably, none of the cytogenetic abnormalities analyzed except coexistence of 13q- and 17p- had a clear impact on the proliferative index of B-CLL cells.
B细胞慢性淋巴细胞白血病(B-CLL)是一种具有明确临床特征且分子和细胞遗传学特征各异的疾病。在此,我们通过对纯化的肿瘤性B-CLL细胞进行间期荧光原位杂交分析,来研究12号染色体三体、13q缺失、17p缺失和11q缺失对其免疫表型、DNA倍体状态及增殖率的影响。总体而言,在研究的180例B-CLL病例中,111例(62%)表现出一种(50%)或多种(12%)基因异常,13q缺失(35%)的检出频率高于12号染色体三体(23%),其次是11q缺失(9%)和17p缺失(8%)。与细胞遗传学未改变的病例相比,12号染色体三体与更高频率的DNA非整倍体、CD19、CD20、CD22、CD24、CD27、CD79b、CD38和sIg的更强表达以及CD43的较低反应性相关。反过来,13q缺失的病例对CD20、FMC7、CD27、CD22、CD5和bcl2的反应性更高,而11q缺失与CD38、FMC7、CD25和sIg的更亮表达相关。对具有细胞遗传学异常的B-CLL病例的免疫表型进行层次聚类分析,可识别出三组不同的患者,其12号染色体三体、11q缺失和13q缺失的频率逐渐增加。值得注意的是,除了13q-和17p-共存外,所分析的细胞遗传学异常均未对B-CLL细胞的增殖指数产生明显影响。