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患者外周血血浆中的循环无细胞 DNA 是多发性骨髓瘤复发的一个信息丰富的生物标志物。

Circulating cell-free DNA in the peripheral blood plasma of patients is an informative biomarker for multiple myeloma relapse.

机构信息

Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Division of Molecular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

出版信息

Int J Clin Oncol. 2021 Nov;26(11):2142-2150. doi: 10.1007/s10147-021-01991-z. Epub 2021 Jul 14.

Abstract

BACKGROUND

Multiple myeloma (MM) is an incurable hematological malignancy. Despite the introduction of several novel drugs, most patients relapse. Biomarkers to identify the early signs of relapse will make it possible to adjust the therapeutic strategy before the disease worsens. Although understanding genetic changes is important for the treatment of MM, currently known biomarkers of relapse, including serum free-light chains and monoclonal paraproteins, are not associated with genetic changes.

METHODS

We therefore performed a multicenter study to examine the usefulness of circulating cell-free DNA (cfDNA) present in the peripheral blood (PB) plasma of patients as a biomarker for MM relapse.

RESULTS

We identified several driver mutations by combined analysis of next-generation sequencing and existing databases of candidate oncogenes. Furthermore, relapse was detected more sensitively by monitoring the circulating cfDNA with these driver mutations than by conventional serum free-light chain examination.

CONCLUSION

These results suggest the potential utility of cfDNA in the PB plasma of patients as a relevant early biomarker for MM relapse.

摘要

背景

多发性骨髓瘤(MM)是一种不可治愈的血液恶性肿瘤。尽管引入了几种新型药物,但大多数患者仍会复发。识别复发早期迹象的生物标志物将使我们有可能在疾病恶化之前调整治疗策略。尽管了解遗传变化对于 MM 的治疗很重要,但目前已知的复发生物标志物,包括血清游离轻链和单克隆副蛋白,与遗传变化无关。

方法

因此,我们进行了一项多中心研究,以研究患者外周血(PB)血浆中存在的循环无细胞 DNA(cfDNA)作为 MM 复发生物标志物的有用性。

结果

通过下一代测序和候选癌基因现有数据库的联合分析,我们鉴定了几种驱动突变。此外,通过监测具有这些驱动突变的循环 cfDNA 比通过常规血清游离轻链检测更敏感地检测到复发。

结论

这些结果表明,患者 PB 血浆中的 cfDNA 作为 MM 复发的相关早期生物标志物具有潜在的应用价值。

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