Michaux L, Wlodarska I, Rack K, Stul M, Criel A, Maerevoet M, Marichal S, Demuynck H, Mineur P, Kargar Samani K, Van Hoof A, Ferrant A, Marynen P, Hagemeijer A
Center for Human Genetics, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
Leukemia. 2005 Jan;19(1):77-82. doi: 10.1038/sj.leu.2403543.
Although reciprocal chromosomal translocations are not typical for B-cell chronic lymphocytic leukemia (B-CLL), we identified the novel t(1;6)(p35.3;p25.2) in eight patients with this disorder. Interestingly, all cases showed lack of somatically mutated IgV(H). Clinical, morphological, immunologic, and genetic features of these patients are described. Briefly, the age ranged from 33 to 81 years (median: 62.5 years) and the sex ratio was 6M:2F. Most of the patients (6/8) presented with advanced clinical stage. Therapy was required in seven cases. After a median follow-up of 28 months, five patients are alive and three died from disease evolution. Three cases developed transformation into diffuse large B-cell lymphoma. Translocation t(1;6) was found as the primary karyotypic abnormality in three patients. Additional chromosomal aberrations included changes frequently found in unmutated B-CLL, that is, del(11)(q), trisomy 12 and 17p aberrations. Fluorescence in situ hybridization analysis performed in seven cases allowed us to map the t(1;6) breakpoints to the 1p35.3 and 6p25.2 chromosomal bands, respectively. The latter breakpoint was located in the genomic region coding for MUM1/IRF4, one of the key regulators of lymphocyte development and proliferation, suggesting involvement of this gene in the t(1;6). Molecular characterization of the t(1;6)(p35.3;p25.2), exclusively found in unmutated subtype of B-CLL, is in progress.
尽管相互染色体易位并非B细胞慢性淋巴细胞白血病（B-CLL）的典型特征，但我们在8例该疾病患者中发现了新的t(1;6)(p35.3;p25.2)。有趣的是，所有病例均显示体细胞突变的IgV(H)缺失。描述了这些患者的临床、形态学、免疫学和遗传学特征。简而言之，患者年龄在33至81岁之间（中位数：62.5岁），性别比为6男:2女。大多数患者（6/8）表现为临床晚期。7例患者需要治疗。中位随访28个月后，5例患者存活，3例死于疾病进展。3例发生转化为弥漫性大B细胞淋巴瘤。在3例患者中发现t(1;6)是主要的核型异常。其他染色体畸变包括在未突变的B-CLL中常见的变化，即del(11)(q)、三体12和17p畸变。对7例患者进行的荧光原位杂交分析使我们能够将t(1;6)断点分别定位到1p35.3和6p25.2染色体带。后一个断点位于编码MUM1/IRF4的基因组区域，MUM1/IRF4是淋巴细胞发育和增殖的关键调节因子之一，提示该基因参与了t(1;6)。仅在未突变的B-CLL亚型中发现的t(1;6)(p35.3;p25.2)的分子特征研究正在进行中。
