Sindelárová Lenka, Michalová Kyra, Zemanová Zuzana, Ransdorfová Sárka, Brezinová Jana, Peková Sona, Schwarz Jirí, Karban Josef, Cmunt Eduard
Center of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, General Faculty Hospital and 1st Medical Faculty, Charles University, U Nemocnice 2, 128 08 Prague 2, Czech Republic.
Cancer Genet Cytogenet. 2005 Jul 1;160(1):27-34. doi: 10.1016/j.cancergencyto.2004.11.004.
B-chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia. Molecular genetic characterization of B-CLL has made significant progress and typical chromosomal anomalies have been assessed. The most frequent chromosomal abnormalities are deletions at 13q14, 17p13, and 11q22 approximately q23 and trisomy 12. The aim of this study was to establish incidence of chromosomal changes in bone marrow or peripheral blood cells (or both) of B-CLL patients using a molecular cytogenetic method, interphase fluorescence in situ hybridization (I-FISH), and to evaluate the prognostic implications. We performed I-FISH on bone marrow and blood smears from 217 B-CLL patients (124 male, 93 female). Trisomy 12 was found in 35 of the 217 (16%); deletion 13q14 was analyzed in 207 patients and found in 112 (54%). Deletion 17p13 was found in 34 (16%) out of 206 examined. Deletion of 11q23 was analyzed in 56 patients and was present in 7 (12%). Statistical analyses were performed to correlate the molecular-cytogenetic findings with disease status (stable versus progressive), Rai stage, CD38/CD19 antigen coexpression, immunoglobulin variable heavy chain (IgV(H)) mutational pattern, and other clinical and laboratory parameters. No apparent differences in distribution were noted for anomalies +12, del(13)(q14), or del(17)(p13) among patients with stable and progressive disease, and no consistent pattern in the distribution of type of genomic changes were found among various Rai stages and in CD38/CD19-positive or -negative patients. Patients without IgV(H) mutation had a worse prognosis; however, distribution of chromosomal abnormalities identified with FISH was the same for patients with and without IgV(H) mutations.
B 细胞慢性淋巴细胞白血病(B-CLL)是最常见的成人白血病。B-CLL 的分子遗传学特征已取得显著进展,典型的染色体异常已得到评估。最常见的染色体异常是 13q14、17p13 和 11q22 至 q23 区域的缺失以及 12 号染色体三体。本研究的目的是使用分子细胞遗传学方法——间期荧光原位杂交(I-FISH),确定 B-CLL 患者骨髓或外周血细胞(或两者)中染色体变化的发生率,并评估其预后意义。我们对 217 例 B-CLL 患者(124 例男性,93 例女性)的骨髓和血涂片进行了 I-FISH。217 例患者中有 35 例(16%)发现 12 号染色体三体;对 207 例患者分析了 13q14 缺失,其中 112 例(54%)存在该缺失。206 例受检患者中有 34 例(16%)发现 17p13 缺失。对 56 例患者分析了 11q23 缺失,其中 7 例(12%)存在该缺失。进行了统计分析,以将分子细胞遗传学结果与疾病状态(稳定与进展)、Rai 分期、CD38/CD19 抗原共表达、免疫球蛋白重链可变区(IgV(H))突变模式以及其他临床和实验室参数相关联。在疾病稳定和进展的患者中,+12、del(13)(q14)或 del(17)(p13)异常的分布没有明显差异,在不同的 Rai 分期以及 CD38/CD19 阳性或阴性患者中,也未发现基因组变化类型分布的一致模式。无 IgV(H)突变的患者预后较差;然而,FISH 检测到的染色体异常分布在有和无 IgV(H)突变的患者中是相同的。