Stilgenbauer S, Döhner K, Bentz M, Lichter P, Döhner H
Medizinische Klinik and Poliklinik V, University of Heidelberg, Germany.
Ann Hematol. 1998 Mar-Apr;76(3-4):101-10. doi: 10.1007/s002770050373.
The genetic alterations underlying the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) are difficult to assess. Cytogenetic studies are hindered by the low in vitro mitotic activity of the tumor cells and the limited resolution of chromosome banding. Molecular genetic analyses are hampered by nonclonal cells contained in the specimens and by the limited knowledge of candidate genes involved. As a complement to cytogenetic and molecular genetic techniques, fluorescence in situ hybridization (FISH) has proven powerful in the molecular cytogenetic analysis of B-CLL. FISH allows the detection of aberrations such as trisomies, deletions, and translocation breakpoints on the single cell level in dividing as well as non-dividing cells without the prerequisite of detailed physical maps or knowledge of involved genes. As detected by the interphase cytogenetic FISH approach, the most common chromosome abnormalities of B-CLL are deletions in band 13q14, followed by deletions in 11q22-q23, trisomy 12, deletions in 17p13, and deletions in 6q21. Abnormalities in 17p13 seem to involve the TP53 tumor suppressor gene, but as yet no candidate genes have been identified for the other frequent aberrations. Toward the identification of such genes by positional cloning, FISH can be applied for detailed aberration mapping at the molecular level. Furthermore, the accurate detection of chromosome aberrations in B-CLL by FISH provides a valid basis for the evaluation of their prognostic significance. Inactivation of TP53 in 17p13 and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors. Genetic abnormalities may eventually provide biological parameters, allowing a risk assessment for individual patients at the time of diagnosis of this clinically heterogeneous disease.
B 细胞慢性淋巴细胞白血病（B-CLL）发病机制背后的基因改变难以评估。细胞遗传学研究受到肿瘤细胞体外有丝分裂活性低以及染色体显带分辨率有限的阻碍。分子遗传学分析则受到标本中包含的非克隆细胞以及对相关候选基因了解有限的影响。作为细胞遗传学和分子遗传学技术的补充，荧光原位杂交（FISH）已被证明在 B-CLL 的分子细胞遗传学分析中具有强大作用。FISH 能够在单细胞水平检测诸如三体、缺失和易位断点等畸变，无论是在分裂细胞还是非分裂细胞中，都无需详细的物理图谱或对相关基因的了解。通过间期细胞遗传学 FISH 方法检测到，B-CLL 最常见的染色体异常是 13q14 带的缺失，其次是 11q22 - q23 的缺失、三体 12、17p13 的缺失以及 6q21 的缺失。17p13 的异常似乎涉及 TP53 肿瘤抑制基因，但对于其他常见畸变，尚未鉴定出候选基因。为了通过定位克隆鉴定此类基因，FISH 可用于分子水平的详细畸变图谱绘制。此外，通过 FISH 准确检测 B-CLL 中的染色体畸变，为评估其预后意义提供了有效的依据。17p13 中 TP53 的失活以及 11q22 - q23 的缺失已被证明是最重要的独立预后因素之一。基因异常最终可能提供生物学参数，以便在诊断这种临床异质性疾病时对个体患者进行风险评估。
