al Saati T, Galoin S, Roda D, Huynh A, Attal M, Delsol G
Laboratoire d'anatomie pathologique et UPCM/CNRS, CHU-Purpan, Toulouse, France.
Bull Cancer. 1998 Oct;85(10):847-54.
Follicular lymphoma constitutes 30-40% of non-Hodgkin's lymphomas. Most patients have widespread disease at diagnosis. The clinical course is generally indolent, and it is not usually curable with available treatment. The source of relapse in patients who achieve complete clinical remission is residual neoplastic cells that are present below the limits of detection using standard techniques. With the development of PCR technology, the presence of these residual malignant cells [Minimal Residual Disease (MRD)] has been demonstrated clearly. Recently, an association of high-dose chemotherapy with autologous bone marrow or peripheral blood progenitor cell autograft appeared promising in the treatment of these lymphomas. In the search of clonal markers for the detection of MRD in follicular lymphomas, two strategies can be used. In the cases associated with the t(14;18) (q32;q21) chromosomal translocation, the bcl-2/JH junctional regions are amplified by PCR in approximately equal to 50% of cases and then sequenced in order to synthesize an anti-junction oligonucleotide probe specific for each patient's malignant clone (clonospecific probe). In the cases negative for this translocation, an alternative strategy consists in the amplification of immunoglobulin high chain (IgH) gene rearrangement (approximately equal to 75% of cases). The present review highlights the value of molecular markers such as bcl-2/JH and VH/JH rearrangements to follow the neoplastic clone and to detect MRD in patients with follicular lymphomas.
滤泡性淋巴瘤占非霍奇金淋巴瘤的30%-40%。大多数患者在诊断时已有广泛病变。其临床病程通常较为惰性,现有治疗方法一般无法治愈。临床完全缓解的患者复发的根源是使用标准技术检测不到的残留肿瘤细胞。随着聚合酶链反应(PCR)技术的发展,这些残留恶性细胞[微小残留病(MRD)]的存在已得到明确证实。最近,大剂量化疗联合自体骨髓或外周血祖细胞自体移植在这些淋巴瘤的治疗中显示出前景。在寻找用于检测滤泡性淋巴瘤MRD的克隆标志物时,可采用两种策略。在与t(14;18) (q32;q21)染色体易位相关的病例中,约50%的病例通过PCR扩增bcl-2/JH连接区,然后进行测序,以合成针对每个患者恶性克隆的抗连接寡核苷酸探针(克隆特异性探针)。在该易位阴性的病例中,另一种策略是扩增免疫球蛋白重链(IgH)基因重排(约75%的病例)。本综述强调了诸如bcl-2/JH和VH/JH重排等分子标志物在追踪肿瘤克隆以及检测滤泡性淋巴瘤患者MRD方面的价值。