Zhu D, Hawkins R E, Hamblin T J, Stevenson F K
Tenovus Laboratory, Southampton University Hospitals.
Br J Haematol. 1994 Mar;86(3):505-12. doi: 10.1111/j.1365-2141.1994.tb04780.x.
The variable region genes used to encode the immunoglobulin expressed by tumour cells of a patient with follicular lymphoma have been identified and sequenced. Initially, a lymph node biopsy was analysed and revealed usage of VH and V kappa genes which had numerous substitutions as compared with the closest germ line genes. The pattern of mutations in VH was consistent with a role for positive selection by antigen. In addition, there was evidence in both VH and V kappa sequences for clonal heterogeneity. After 5 years, which included treatment with chemotherapy, the patient relapsed with tumour cells present in the blood. Analysis of the V-genes used by the emerging tumour revealed a single homogeneous sequence for both VH and VL, which, in each case, matched closely one of the sequences in the original lymph node biopsy. These results indicate that selection, possibly mediated by antigen, can operate on a cell destined to give rise to lymphoma, and that intraclonal variation can occur after the neoplastic event. However, in this case, late relapse in the blood is dominated by a single clone.
已鉴定并测序了用于编码滤泡性淋巴瘤患者肿瘤细胞所表达免疫球蛋白的可变区基因。最初，对一份淋巴结活检样本进行分析，结果显示VH和Vκ基因的使用情况，与最接近的种系基因相比，这些基因有大量替换。VH中的突变模式与抗原阳性选择的作用一致。此外，在VH和Vκ序列中均有克隆异质性的证据。5年后，包括化疗在内的治疗过程中，患者复发，血液中出现肿瘤细胞。对新出现肿瘤所使用的V基因进行分析，结果显示VH和VL均为单一的同源序列，且在每种情况下，都与原始淋巴结活检中的一个序列紧密匹配。这些结果表明，可能由抗原介导的选择作用，可作用于注定会引发淋巴瘤的细胞，并且肿瘤形成事件后可发生克隆内变异。然而，在这种情况下，血液中的晚期复发以单个克隆为主。
