Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Spain.
Department of Medicine, University of Salamanca and University Hospital of Salamanca-IBSAL, Salamanca, Spain.
Br J Haematol. 2018 Apr;181(1):11-26. doi: 10.1111/bjh.15075. Epub 2017 Dec 19.
Despite the significantly higher complete remission rates and improved survival achieved in the last decade, multiple myeloma (MM) patients continue to relapse due to persistence of minimal residual disease (MRD). Generally, MRD refers to persistence of low levels of disease in the order of one tumour cell in ≥10 normal cells. Currently, molecular and immunophenotypic techniques are employed for MRD detection. This review focuses on MRD detection by molecular techniques, including allele-specific oligonucleotide polymerase chain reaction (ASO-PCR), next-generation sequencing (NGS) and digital PCR (dPCR), in addition to a brief description of, and comparison with, multiparameter flow cytometry. The basic principles, technical advantages and limitations, and the clinical impact of all three molecular techniques are reviewed and compared. They all have a sensitivity of at least 10 , among which ASO real-time quantitative PCR is the most well-standardized, and NGS carries the highest sensitivity and applicability, while dPCR is still under investigation. Furthermore, molecular MRD negativity is a favourable prognostic factor for survival of patients with MM. However, several challenges inherent to molecular detection of MRD still remain to be overcome, particularly false negativity and failure to detect extramedullary disease. Finally, detection of MRD from peripheral blood remains challenging.
尽管在过去十年中，多发性骨髓瘤 (MM) 患者的完全缓解率和生存率显著提高，但由于微小残留病 (MRD) 的持续存在，仍会复发。通常，MRD 是指在≥10 个正常细胞中存在低水平疾病的持续存在，数量为一个肿瘤细胞。目前，采用分子和免疫表型技术进行 MRD 检测。本综述重点介绍了分子技术检测 MRD 的方法，包括等位基因特异性寡核苷酸聚合酶链反应 (ASO-PCR)、下一代测序 (NGS) 和数字 PCR (dPCR)，并简要描述了多参数流式细胞术，并对其进行了比较。综述并比较了这三种分子技术的基本原理、技术优势和局限性，以及临床影响。它们的灵敏度至少为 10，其中 ASO 实时定量 PCR 最标准化，NGS 具有最高的灵敏度和适用性，而 dPCR 仍在研究中。此外，分子 MRD 阴性是 MM 患者生存的有利预后因素。然而，分子检测 MRD 中仍存在一些固有的挑战，特别是假阴性和无法检测骨髓外疾病。最后，外周血中的 MRD 检测仍然具有挑战性。
