Novel treatment in multiple myeloma represented by proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies have produced a deep response. However, relapses are possible, and all classes of drugs are refractory to patients. Next-generation sequencing has improved our understanding of the multiple myeloma genome related to drug resistance and has discovered many genomic variants. Therefore, this study was conducted to investigate new variants associated with drug resistance in MM patients who relapsed and refractory to bortezomib regimen and daratumumab treatment using next-generation sequencing for whole-exome sequencing. Peripheral blood samples were collected in EDTA tubes from six patients; four were in relapsed and refractory to bortezomib regimens and daratumumab; two patients responded to bortezomib regimens. Whole-exome sequencing was performed by the MGI-DNBSEQ-G400 instrument. We identified 21 variants in multiple myeloma patients. Seventeen variants were found in relapsed and refractory multiple myeloma in 11 genes (GNAQ, PMS1, CREB1, NSUNS2, PIK3CG, ROS1, PMS2, FIT4, KDM5A, STK11 and ZFHX3). And four variants were identified in two patients with response to bortezomib regimens in 4 genes (RAF1, CREB1, ZFHX3 and INSR). We have observed several genetic variants in many genes that may have been associated with the poor prognosis and poor response to treatment in these patients. These values should be further confirmed in large sample studies using the RNA-seq technique to identify genome expression.

以蛋白酶体抑制剂、免疫调节药物和单克隆抗体为代表的多发性骨髓瘤新疗法已经产生了深刻的反应。然而，复发是可能的，并且所有类别的药物对患者都是难治的。下一代测序提高了我们对与耐药性相关的多发性骨髓瘤基因组的理解，并发现了许多基因组变异。因此，本研究旨在使用下一代测序进行全外显子组测序，研究与硼替佐米方案和达雷妥尤单抗治疗复发和难治的 MM 患者的耐药性相关的新变异。从 6 名患者的 EDTA 试管中采集外周血样本；4 例复发且对硼替佐米方案和达雷妥尤单抗无效；两名患者对硼替佐米方案有反应。全外显子组测序由 MGI-DNBSEQ-G400 仪器进行。我们在多发性骨髓瘤患者中发现了 21 种变异。在 11 个基因的复发和难治性多发性骨髓瘤中发现了 17 个变异（GNAQ、PMS1、CREB1、NSUNS2、PIK3CG、ROS1、PMS2、FIT4、KDM5A、STK11和ZFHX3）。并且在 4 个基因（RAF1、CREB1、ZFHX3和INSR）中对 bortezomib 方案有反应的两名患者中发现了四种变异。我们已经观察到许多基因中的几种遗传变异，这些变异可能与这些患者的不良预后和对治疗的不良反应有关。这些值应该在使用RNA-seq技术鉴定基因组表达的大样本研究中得到进一步证实。