非霍奇金淋巴瘤bcl-2／IgH基因重排及微小残留病变的检测

探索bcl-2基因重排在非霍奇金淋巴瘤(NHL)的发生及演变中的作用,以bcl-2/IgH重排为克隆标志,建立敏感的检测淋巴瘤微小残留病变的方法。用多聚酶链反应(PCR)检测bcl-2/IgH基因重排,用系列稀释试验检测该方法的灵敏度。经检测9种恶性淋巴瘤细胞系中Su-DHL-4和Su-DHL-6有bcl-2/IgH基因重排,用系列稀释试验检测该方法的灵敏度为1:10~5。29例NHL石蜡包埋的组织标本中,共检出6例有bcl-2基因重排,其中滤泡型NHL(F-NHL)4例(36.4％),弥漫型NHL(D-NHL)2例(18.2％),全部在B细胞性NHL中检出。16例F-NHL患者中,4例外周血和骨髓中同时检出bcl-2(MBR)/IgH基因重排,化疗达CR后依然存在。结论提示,bcl-2基因重排主要与低度恶性的B细胞性淋巴瘤有关,重排方式以bcl-2(MBR)/IgH为主。bcl-2基因重排的检测为对滤泡性淋巴瘤微小残留病变的检测提供了一个快速、敏感、特异的方法,对该疾病的分期、疗效和预后的评估有一定的临床价值。

bcl-2/IgH Gene Rearrangement and Detection of Minimal Residual Disease in Non-Hodgkin's Lymphoma

To elucidate the role and the significance of bcl-2/IgH gene rearrangement in tumorigenesis, development and therapy of non-Hodgkin' s lymphoma ( NHL), the polymerase chain reaction ( PCR) to detect bcl-2 gene rearrangement and the serial dilution method to define the sensitivity of PCR were used. In 9 different lymphoma cell lines, Su-DHL-4 and Su-DHL-6 showed bcl-2/IgH gene rearrangement, the sensitivity of PCR was 10-5 times. In paraffin-embedded tissue specimens of 29 cases with NHL, 6 cases demonstrated bcl-2/IgH rearrangement including 4 of 11 cases of follicular NHL(F-NHL) and 2 of 11 cases of diffuse NHL(D-NHL). These PCR positive cases were B-cell NHL. In bone marrow and peripheral blood samples of 16 patients with F-NHL, 4 cases were PCR positive at initial diagnosis and after complete remission (CR) .It is concluded that bcl-2/IgH gene rearrangement is mainly associated with low-grade B-cell NHL. The main pattern of bcl-2 rearrangements is MBR-IgH. Detection of bcl-2 rearrangement by PCR provides a sensitive and specific assay for minimal residual disease in cases with F-NHL. It helps to improve staging of diasase, evaluation of treatment and prognosis.