Oscier D G
Department of Haematology, Royal Bournemouth Hospital, UK.
Blood Rev. 1994 Jun;8(2):88-97. doi: 10.1016/s0268-960x(05)80013-x.
Genetic abnormalities are found in 50% of cases of chronic lymphocytic leukaemia (CLL) by cytogenetic analysis and in a higher percentage of patients using molecular techniques. The commonest cytogenetic abnormalities are trisomy 12 and deletions or translocations of the long arm of chromosome 13 usually involving band q14. The genetic consequences of trisomy 12 are unknown but structural abnormalities of chromosome 13q14 frequently involve hetero or homozygous loss of a region distal to the retinoblastoma gene which may be the site of a tumour suppressor gene. Trisomy 12 or loss of one copy of the retinoblastoma gene have been detected by fluorescent in situ hybridisation (FISH) in interphase cells of patients with a normal karyotype. By combining FISH with immunophenotyping, it has been found that trisomy 12 occurs in only 30 to 40% of the malignant clone, suggesting that it is a secondary event in leukaemogenesis. Trisomy 12 is strongly associated with atypical lymphocyte morphology in patients with otherwise typical CLL. Complex karyotypic abnormalities, a high percentage of abnormal metaphases and trisomy 12 but not structural abnormalities of chromosome 13 are associated with a poor prognosis at all stages of the disease. Mutations or deletions of the P53 gene are found in 10 to 15% of patients with advanced CLL and correlate with resistance to treatment and poor survival.
通过细胞遗传学分析，在50%的慢性淋巴细胞白血病（CLL）病例中发现了基因异常，而使用分子技术检测时，这一比例在患者中更高。最常见的细胞遗传学异常是12号染色体三体以及13号染色体长臂的缺失或易位，通常涉及14q12带。12号染色体三体的遗传学后果尚不清楚，但13q14染色体的结构异常常常涉及视网膜母细胞瘤基因远端区域的杂合或纯合缺失，该区域可能是一个肿瘤抑制基因的位点。通过荧光原位杂交（FISH）在核型正常患者的间期细胞中检测到了12号染色体三体或视网膜母细胞瘤基因一个拷贝的缺失。通过将FISH与免疫表型分析相结合，发现12号染色体三体仅发生在30%至40%的恶性克隆中，这表明它是白血病发生过程中的一个继发事件。在具有典型CLL的患者中，12号染色体三体与非典型淋巴细胞形态密切相关。复杂的核型异常、高比例的异常中期以及12号染色体三体而非13号染色体的结构异常与疾病各阶段的不良预后相关。在10%至15%的晚期CLL患者中发现了P53基因的突变或缺失，这与治疗耐药性和不良生存相关。
