Cole-Sinclair M, Foroni L, Wright F, Mehta A, Prentice H G, Hoffbrand A V
Department of Haematology, Royal Free Hospital School of Medicine, London, United Kingdom.
Leuk Lymphoma. 1993;11 Suppl 2:49-58. doi: 10.3109/10428199309064262.
Rearrangement of the immunoglobulin heavy chain (IgH) gene can be utilized as a marker of clonality in a number of B-lineage lymphoproliferative disorders including acute lymphoblastic leukaemia (ALL). We have used a PCR technique involving a panel of amplimers for the 6 different Variable (VH) region families and for a consensus sequence of the Joining (JH) segment to detect clonal IgH rearrangements in the peripheral blood (PB) and/or bone marrow (BM) of 28 patients (17 children and 11 adults) with B-lineage ALL at presentation (20 patients) or with overt relapse (8 patients). The age range of the patients was 2-65 years (mean 15.7 years). Follow up remission BM samples were analysed in 22 patients during and after therapy (2-7 samples per patient), 1-50 months after presentation or relapse. In 1 relapsed case, previously stored complete remission (CR) samples were analysed retrospectively. Clonal IgH chain rearrangements were detected by PCR in 90% of patients studied initially. The 2 VH region families most commonly used were the large VH3 family (65%) and the smaller more JH-proximal VH4 family (22%). More than one VH clone was detectable in 25% of the cases. A gene "fingerprinting" modification of a previously described method was applied to the detection of minimal residual disease (MRD) in follow up BM samples with a sensitivity of 10(-3) to 10(-4). In 8 of 14 patients remaining in complete remission (CR) during the time of study, all PCR analyses on BM samples in the first 6 months were negative, in some cases as early as 2 weeks post-induction therapy, and a further patient reverted from being PCR positive in the first month after the commencement of therapy to sustained PCR negativity. One adult remains in CR at 50 months after presentation and has been PCR negative at 2 time points after cessation of maintenance therapy (30 and 50 months). Eight patients relapsed in the study period comprising 6 BM and 2 isolated CNS relapses. In 4 cases of BM relapse occurring within 7 months of the start of therapy, all BM remission samples tested in this period were PCR positive. In 2 other patients BM samples tested 7 and 2 months respectively prior to relapse were PCR negative. In the 2 patients with isolated CNS relapse, PCR of BM samples from 2 and 10 months before the relapse were negative.(ABSTRACT TRUNCATED AT 400 WORDS)
免疫球蛋白重链（IgH）基因重排可作为多种B淋巴细胞增殖性疾病（包括急性淋巴细胞白血病（ALL））克隆性的标志物。我们采用了一种聚合酶链反应（PCR）技术，该技术涉及一组针对6个不同可变区（VH）家族以及连接区（JH）片段共有序列的扩增引物，以检测28例B系ALL患者（17例儿童和11例成人）初诊时（20例患者）或明显复发时（8例患者）外周血（PB）和/或骨髓（BM）中的克隆性IgH重排。患者年龄范围为2至65岁（平均15.7岁）。对22例患者治疗期间及治疗后（每位患者2至7份样本）、初诊或复发后1至50个月的缓解期骨髓样本进行了分析。在1例复发病例中，对先前储存的完全缓解（CR）样本进行了回顾性分析。通过PCR在最初研究的90%患者中检测到克隆性IgH链重排。最常使用的2个VH区域家族是较大的VH3家族（65%）和较小且更靠近JH的VH4家族（22%）。25%的病例中可检测到不止一个VH克隆。将先前描述方法的基因“指纹识别”改进应用于随访骨髓样本中微小残留病（MRD）的检测，灵敏度为10^(-3)至10^(-4)。在研究期间仍处于完全缓解（CR）的14例患者中的8例，最初6个月对骨髓样本的所有PCR分析均为阴性，在某些情况下早在诱导治疗后2周即为阴性，另有1例患者在治疗开始后第一个月从PCR阳性转变为持续PCR阴性。1例成人患者初诊后50个月仍处于CR状态，维持治疗停止后2个时间点（30和50个月）PCR均为阴性。8例患者在研究期间复发，包括6例骨髓复发和2例孤立的中枢神经系统复发。在治疗开始后7个月内发生的4例骨髓复发病例中，该期间检测的所有骨髓缓解样本PCR均为阳性。在另外2例患者中，复发前7个月和2个月检测的骨髓样本PCR均为阴性。在2例孤立的中枢神经系统复发患者中，复发前2个月和10个月的骨髓样本PCR均为阴性。（摘要截取自400字）
