Horning S J, Galili N, Cleary M, Sklar J
Department of Medicine, Stanford University Medical Center, CA.
Blood. 1990 Mar 1;75(5):1139-45.
Analysis of immunoglobulin (Ig) and T-cell receptor gene rearrangements, using Southern blot hybridization, has been applied to peripheral blood lymphocytes (PBL) in 335 samples from patients with non-Hodgkin's lymphoma. The incidence of circulating lymphoma cells detected by gene rearrangement analyses is related to the histologic subtype, clinical stage of disease, and clinical status. Among 104 patients studied at diagnosis, the incidence of positive analyses was 34% in low-grade lymphoma and only 8% in intermediate-grade lymphoma. Clonal Ig gene rearrangements were detected nearly universally in the small lymphocytic histologic subtype. PBL studies were related to the initial stage of disease: positive studies were seen in 35% of patients with stage IV disease, 29% of patients with stage III disease, and 12% of patients with stages I-II disease. The incidence of PBL rearrangements at the time of disease recurrence in 32 patients requiring cytoreductive therapy was 48%, somewhat greater than at initial diagnosis. A group of patients with low-grade lymphoma, who had treatment deferred after diagnosis or recurrence, was also studied; the incidence of PBL rearrangements was 38% in this population. Among 157 patients clinically free of disease, DNA analyses of the PBL were positive in only 10%. Subsequent relapse of disease in 26 patients was antedated by PBL rearrangement in only one patient. Clonal rearrangements detected in 15 patients have been followed by recurrence of clinical disease in only one patient over a median of 24 months from the time of analysis. The lack of detectable rearrangements in the peripheral blood in the majority of patients may be due to methodology or the biology of the disease. These issues may be further addressed with alternative methods for assessment of minimal disease. However, rigorous testing of any new molecular tool requires an adequate patient population in which disease status is closely monitored over a sufficient period of time.
利用Southern印迹杂交分析免疫球蛋白（Ig）和T细胞受体基因重排，已应用于335例非霍奇金淋巴瘤患者的外周血淋巴细胞（PBL）检测。通过基因重排分析检测到的循环淋巴瘤细胞发生率与组织学亚型、疾病临床分期及临床状态相关。在104例诊断时接受研究的患者中，低度淋巴瘤患者基因重排分析阳性率为34%，中度淋巴瘤患者仅为8%。在小淋巴细胞组织学亚型中几乎普遍检测到克隆性Ig基因重排。PBL研究与疾病的初始阶段相关：IV期疾病患者中35%检测为阳性，III期疾病患者中29%检测为阳性，I-II期疾病患者中12%检测为阳性。32例需要减瘤治疗的患者疾病复发时PBL重排发生率为48%，略高于初始诊断时。还对一组诊断或复发后推迟治疗的低度淋巴瘤患者进行了研究；该人群中PBL重排发生率为38%。在157例临床无病患者中，PBL的DNA分析仅10%为阳性。26例患者随后疾病复发，仅有1例患者在复发前出现PBL重排。在15例患者中检测到的克隆性重排，自分析之时起中位24个月期间，仅有1例患者随后出现临床疾病复发。大多数患者外周血中未检测到重排可能是由于方法学问题或疾病生物学特性。这些问题可通过评估微小疾病的替代方法进一步探讨。然而，对任何新的分子工具进行严格测试都需要有足够数量的患者群体，并在足够长的时间内密切监测疾病状态。
