Juliusson G, Oscier D G, Fitchett M, Ross F M, Stockdill G, Mackie M J, Parker A C, Castoldi G L, Guneo A, Knuutila S, Elonen E, Gahrton G
Department of Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
N Engl J Med. 1990 Sep 13;323(11):720-4. doi: 10.1056/NEJM199009133231105.
Specific chromosomal abnormalities have been shown to affect the overall survival of patients with acute leukemia, but the possibility that specific chromosomal defects may influence the course of B-cell chronic lymphocytic leukemia (CLL) is controversial. We assessed this possibility as follows: blood mononuclear cells from 433 patients with B-cell CLL in five European centers were cultured with B-cell mitogens, and banded metaphases were studied.
Three hundred ninety-one patients could be evaluated cytogenetically, and 218 had clonal chromosomal changes. The most common abnormalities were trisomy 12 (n = 67) and structural abnormalities of chromosome 13 (n = 51; most involving the site of the retinoblastoma gene) and of chromosome 14 (n = 41). Patients with a normal karyotype had a median overall survival of more than 15 years, in contrast to 7.7 years for patients with clonal changes. Patients with single abnormalities (n = 113) did better than those with complex karyotypes (P less than 0.001). Patients with abnormalities involving chromosome 14q had poorer survival than those with aberrations of chromosome 13q (P less than 0.05). Among patients with single abnormalities, those with trisomy 12 alone had poorer survival than patients with single aberrations of chromosome 13q (P = 0.01); the latter had the same survival as those with a normal karyotype. A high percentage of cells in metaphase with chromosomal abnormalities, indicating highly proliferative leukemic cells, was associated with poor survival (P less than 0.001). Cox proportional-hazards analysis identified age, sex, the percentage of cells in metaphase with chromosomal abnormalities, and the clinical stage of the disease (Binet classification system) as independent prognostic variables.
Chromosomal analysis provides prognostic information about overall survival in addition to that supplied by clinical data in patients with B-cell CLL.
特定的染色体异常已被证明会影响急性白血病患者的总生存期，但特定染色体缺陷可能影响B细胞慢性淋巴细胞白血病（CLL）病程的可能性存在争议。我们通过以下方式评估了这种可能性：来自欧洲五个中心的433例B细胞CLL患者的血液单核细胞用B细胞有丝分裂原进行培养，并对显带中期染色体进行研究。
391例患者可进行细胞遗传学评估，其中218例有克隆性染色体改变。最常见的异常是12号染色体三体（n = 67）以及13号染色体（n = 51；大多数涉及视网膜母细胞瘤基因位点）和14号染色体（n = 41）的结构异常。核型正常的患者中位总生存期超过15年，而有克隆性改变的患者为7.7年。单一异常的患者（n = 113）比核型复杂的患者预后更好（P < 0.001）。涉及14q染色体的异常患者比13q染色体畸变患者生存期更短（P < 0.05）。在单一异常的患者中，单纯12号染色体三体的患者比13q染色体单一畸变的患者生存期更短（P = 0.01）；后者与核型正常的患者生存期相同。中期染色体异常细胞的高比例表明白血病细胞增殖活跃，这与生存期较差相关（P < 0.001）。Cox比例风险分析确定年龄、性别、中期染色体异常细胞的百分比以及疾病的临床分期（Binet分类系统）为独立的预后变量。
除了临床数据提供的信息外，染色体分析还能为B细胞CLL患者的总生存期提供预后信息。
