Auer Rebecca L, Riaz Sophia, Cotter Finbarr E
Centre for Haematology, Institute of Cell and Molecular Science, Barts & The London, Queen Mary's School of Medicine, 4 Newark Street, London, UK.
Br J Haematol. 2007 Jun;137(5):443-53. doi: 10.1111/j.1365-2141.2007.06600.x.
Loss of the long arm of chromosomes 11 and 13 is the most consistent cytogenetic abnormalities for patients with B-cell chronic lymphocytic leukaemia (B-CLL). They suggest the presence of as yet unidentified tumour suppressor genes within well-defined minimal-deleted regions (MinDRs). We have identified 38 orthologues of the human genes in MinDRs in zebrafish cDNA and syntenic regions for the human deletions in the zebrafish genome. One region on chromosome 9 in the zebrafish genome is of potential interest. Within chromosome 9, five genes and two microRNAs were identified with shared synteny to the MinDRs in B-CLL (two genes to human chromosome 11, three to human chromosome 13 and two chromosome 13 microRNAs). The critical region on zebrafish chromosome 9 maps to the MinDR for both human chromosomes, suggesting a common ancestry for B-CLL tumour suppressor genes. Target-selected mutagenesis to identify zebrafish mutants with knock-outs of genes in this region will allow analysis of their in vivo potential for lymphoproliferation and may define causative genes for B-CLL within human chromosomes 11q and 13q. Our study provides an explanation for involvement of both 11q and 13q in B-CLL and the potential to develop animal models for this common lymphoproliferative disorder.
11号和13号染色体长臂缺失是B细胞慢性淋巴细胞白血病（B-CLL）患者最一致的细胞遗传学异常。它们提示在明确界定的最小缺失区域（MinDRs）内存在尚未鉴定的肿瘤抑制基因。我们已在斑马鱼cDNA的MinDRs以及斑马鱼基因组中人类缺失区域的同线区域中鉴定出38个人类基因的直系同源物。斑马鱼基因组9号染色体上的一个区域具有潜在研究价值。在9号染色体上，鉴定出了五个基因和两个微小RNA，它们与B-CLL中的MinDRs具有共同的同线性（两个基因与人类11号染色体同线，三个与人类13号染色体同线，两个微小RNA与13号染色体同线）。斑马鱼9号染色体上的关键区域与两个人类染色体的MinDRs相对应，提示B-CLL肿瘤抑制基因具有共同的祖先。通过靶向选择诱变来鉴定该区域基因敲除的斑马鱼突变体，将有助于分析它们在体内的淋巴细胞增殖潜能，并可能确定人类11号和13号染色体上B-CLL的致病基因。我们的研究为11号和13号染色体在B-CLL中的作用提供了解释，并为这种常见的淋巴细胞增殖性疾病开发动物模型提供了可能性。
