Dierlamm J, Michaux L, Criel A, Wlodarska I, Van den Berghe H, Hossfeld D K
Center for Human Genetics, University of Leuven, Belgium.
Cancer Genet Cytogenet. 1997 Mar;94(1):27-35. doi: 10.1016/s0165-4608(96)00246-4.
Clonal chromosome abnormalities can be detected in approximately 50% of patients with chronic lymphocytic leukemia (CLL). The most common changes are trisomy 12, followed by structural abnormalities of 13q, 11q, 6q, and 14q. By fluorescence in situ hybridization (FISH), these aberrations can be demonstrated even in cases with insufficient mitotic yield or a normal karyotype. The biologic consequences of trisomy 12 are unknown, but a gene dosage effect is suspected and studies on partial trisomy 12 indicate that the region 12q13 to 12q22 might be of particular pathogenetic importance. Trisomy 12 is strongly associated with atypical lymphocyte morphology and seems to be a secondary event in leukemogenesis, as shown by combined immunophenotyping and interphase FISH. Structural abnormalities of 13q frequently involve hetero- and homozygous deletions of a region in 13q14, distal to the retinoblastoma gene, which may be the site of a tumor suppressor gene. In contrast to a normal karyotype or structural changes of 13q, complex karyotypic abnormalities, high percentage of abnormal metaphases, trisomy 12 and structural changes involving the P53 tumor suppressor gene on 17p13 are adverse prognostic indicators. Cytogenetic and molecular findings provide important diagnostic, clinical, and prognostic information which can contribute to treatment decisions and follow-up of CLL patients.
在大约50%的慢性淋巴细胞白血病（CLL）患者中可检测到克隆性染色体异常。最常见的变化是12号染色体三体，其次是13q、11q、6q和14q的结构异常。通过荧光原位杂交（FISH），即使在有丝分裂产量不足或核型正常的病例中也能证实这些畸变。12号染色体三体的生物学后果尚不清楚，但怀疑存在基因剂量效应，对12号染色体部分三体的研究表明，12q13至12q22区域可能具有特殊的致病重要性。12号染色体三体与非典型淋巴细胞形态密切相关，似乎是白血病发生过程中的继发事件，联合免疫表型分析和间期FISH已证实这一点。13q的结构异常常涉及视网膜母细胞瘤基因远端13q14区域的杂合性和纯合性缺失，该区域可能是一个肿瘤抑制基因的位点。与正常核型或13q的结构改变相反，复杂核型异常、高比例的异常中期、12号染色体三体以及涉及17p13上P53肿瘤抑制基因的结构改变是不良预后指标。细胞遗传学和分子学发现提供了重要的诊断、临床和预后信息，有助于CLL患者的治疗决策和随访。
