Sato Masahiko, Yamazaki Jumpei, Goto-Koshino Yuko, Setoguchi Asuka, Takahashi Masashi, Baba Kenji, Fujino Yasuhito, Ohno Koichi, Tsujimoto Hajime
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Laboratory of Molecular Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.
Vet J. 2016 Sep;215:38-42. doi: 10.1016/j.tvjl.2016.05.012. Epub 2016 May 26.
Lymphoma is the most common haematopoietic malignancy in dogs. Since a high proportion of dogs with lymphoma achieve remission soon after initiation of chemotherapy, an objective marker assessing treatment efficacy is required. Following clinical remission, the residual population of tumour cells can be referred to as the minimal residual disease (MRD). MRD traditionally has been detected by cytology and flow cytometry; however, if the burden of malignant cells is low, these methods might not be sufficiently sensitive to detect MRD. As an extension of the development of PCR for antigen receptor gene rearrangements (PARR) in dogs, there has been recent progress in the application of real-time quantitative PCR (RT-qPCR) to canine lymphoma. With the RT-qPCR system, a very high sensitivity (1 cell per 10,000 cells) has been achieved by preparing allele-specific oligonucleotide primers and probes designed from neoplastic clones of each dog. A series of MRD diagnostics studies employing the RT-qPCR system has revealed its usefulness as a prognostic indicator, an objective marker of treatment efficacy and a predictor of relapse for dogs with lymphoma receiving chemotherapy. Introduction of the MRD monitoring system will provide an innovative scientific tool in the development of superior treatments and monitoring strategies for canine lymphoma.
淋巴瘤是犬类中最常见的造血系统恶性肿瘤。由于高比例的淋巴瘤犬在化疗开始后不久即可实现缓解，因此需要一种评估治疗效果的客观标志物。临床缓解后，肿瘤细胞的残留群体可称为微小残留病（MRD）。传统上，MRD是通过细胞学和流式细胞术检测的；然而，如果恶性细胞负担较低，这些方法可能不足以灵敏地检测到MRD。作为犬类抗原受体基因重排（PARR）的PCR技术发展的延伸，实时定量PCR（RT-qPCR）在犬淋巴瘤中的应用最近取得了进展。利用RT-qPCR系统，通过制备从每只犬的肿瘤克隆设计的等位基因特异性寡核苷酸引物和探针，已实现了非常高的灵敏度（每10,000个细胞中有1个细胞）。一系列采用RT-qPCR系统的MRD诊断研究表明，它可作为接受化疗的淋巴瘤犬的预后指标、治疗效果的客观标志物和复发预测指标。引入MRD监测系统将为犬淋巴瘤的优质治疗和监测策略的开发提供一种创新的科学工具。
