慢性淋巴细胞白血病间期荧光原位杂交检测染色体异常及临床分析

Chromosomal Aberrations in Chronic Lymphocytic Leukemia by Interphase Fluorescence in Situ Hybridization and Their Association with Clinical Features

本研究旨在了解慢性淋巴细胞白血病(CLL)常见染色体异常情况及其与临床指标和疗效的关系。以4种序列特异性探针P53、D13S25、ATM、RB1和1种着丝粒探针CSP12,采用间期荧光原位杂交技术(I-FISH)对10例正常对照者骨髓建立各探针的检测阈值,然后对9例染色体核型分析阴性/无分裂相的CLL患者进行检测,检测结果大于阈值为阳性,小于阈值为阴性。结果表明:用p53与D13S25检测7例患者结果均呈阳性,ATM探针检测5例患者结果呈阳性,用RB1与CSP12探针检测4例患者结果呈阳性。9例患者I-FISH检测结果均显示有遗传学异常。检测显示,ATM缺失与患者血红蛋白水平有显著相关性,ATM缺失阳性的患者更易出现全身广泛淋巴结肿大。结论:I-FISH技术适用于CLL患者的细胞遗传学分析,提高了CLL的染色体异常检出率。但I-FISH检测的细胞遗传学异常是否是CLL患者的重要预后因素,尚需扩大样本量的研究和长期随访观察。

This study was aimed to investigate the common chromosomal aberrations in chronic lymphocytic leukemia （CLL） and to explore the relationship between these chromosomal aberrations and clinical features of CLL. Sequence-specific DNA probes （D13S25, RB1, p53, ATM） and one centromeric probe CSP12 were applied to detect del（ 13q14）, del（17pl3）, del（llq22-q23） and trisomy 12 by using interphase fluorescence in situ hybridization（I- FISH）. 9 CLL patients with negative conventional cytogenetics or without mitotic figure were enrolled in this study. The threshold was established using 10 controls without hematopoietic malignancies. The results indicated that compared with the established threshold, all of the 9 CLL patients showed cytogenetic abnormalities. The detection using p53 and D13S25 showed positive in 7 cases, positive was observed in 5 cases by using ATM and in 4 cases by using both RB1 and CSP12. There was significant correlation between the ATM and the hemoglobin level of the patients. In addition, the elevated probability of gaining bulky lymphadenopathy was found in ATM positive patients. It is concluded that the I-FISH is a more rapid and sensitive technique for analysis of chromosome aberrations in CLL. A large series study with long-term follow-up is needed to reveal the role of cytogenetic abnormalities in the determination of CLL prognosis.