Laboratory Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Clin Chem. 2021 Jun 1;67(6):867-875. doi: 10.1093/clinchem/hvab017.
Due to improved treatment, more patients with multiple myeloma (MM) reach a state of minimal residual disease (MRD). Different strategies for MM MRD monitoring include flow cytometry, allele-specific oligonucleotide-quantitative PCR, next-generation sequencing, and mass spectrometry (MS). The last 3 methods rely on the presence and the stability of a unique immunoglobulin fingerprint derived from the clonal plasma cell population. For MS-MRD monitoring it is imperative that MS-compatible clonotypic M-protein peptides are identified. To support implementation of molecular MRD techniques, we studied the presence and stability of these clonotypic features in the CoMMpass database.
An analysis pipeline based on MiXCR and HIGH-VQUEST was constructed to identify clonal molecular fingerprints and their clonotypic peptides based on transcriptomic datasets. To determine the stability of the clonal fingerprints, we compared the clonal fingerprints during disease progression for each patient.
The analysis pipeline to establish the clonal fingerprint and MS-suitable clonotypic peptides was successfully validated in MM cell lines. In a cohort of 609 patients with MM, we demonstrated that the most abundant clone harbored a unique clonal molecular fingerprint and that multiple unique clonotypic peptides compatible with MS measurements could be identified for all patients. Furthermore, the clonal immunoglobulin gene fingerprints of both the light and heavy chain remained stable during MM disease progression.
Our data support the use of the clonal immunoglobulin gene fingerprints in patients with MM as a suitable MRD target for MS-MRD analyses.
由于治疗的改善，越来越多的多发性骨髓瘤（MM）患者达到微小残留疾病（MRD）状态。MM MRD 监测的不同策略包括流式细胞术、等位基因特异性寡核苷酸定量 PCR、下一代测序和质谱（MS）。后 3 种方法都依赖于从克隆性浆细胞群体中获得的独特免疫球蛋白指纹的存在和稳定性。对于 MS-MRD 监测，必须识别与 MS 兼容的克隆型 M 蛋白肽。为了支持分子 MRD 技术的实施，我们在 CoMMpass 数据库中研究了这些克隆型特征的存在和稳定性。
构建了基于 MiXCR 和 HIGH-VQUEST 的分析管道，以根据转录组数据集识别克隆分子指纹及其克隆型肽。为了确定克隆指纹的稳定性，我们比较了每位患者疾病进展过程中的克隆指纹。
用于建立克隆指纹和 MS 兼容的克隆型肽的分析管道在 MM 细胞系中成功验证。在 609 名 MM 患者的队列中，我们证明最丰富的克隆具有独特的克隆分子指纹，并且可以为所有患者鉴定出多个与 MS 测量兼容的独特克隆型肽。此外，轻链和重链的克隆免疫球蛋白基因指纹在 MM 疾病进展过程中保持稳定。
我们的数据支持将 MM 患者的克隆免疫球蛋白基因指纹用作 MS-MRD 分析的合适 MRD 靶标。
