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液体活检在精准医学时代的多发性骨髓瘤中的应用。

Liquid biopsies for multiple myeloma in a time of precision medicine.

机构信息

Myeloma and Lymphoma Research Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal.

Hemato-Oncology Unit, Myeloma and Lymphoma Research Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal.

出版信息

J Mol Med (Berl). 2020 Apr;98(4):513-525. doi: 10.1007/s00109-020-01897-9. Epub 2020 Apr 4.

Abstract

Multiple myeloma (MM) is a challenging, progressive, and highly heterogeneous hematological malignancy. MM is characterized by multifocal proliferation of neoplastic plasma cells in the bone marrow (BM) and sometimes in extramedullary organs. Despite the availability of novel drugs and the longer median overall survival, some patients survive more than 10 years while others die rapidly. This heterogeneity is mainly driven by biological characteristics of MM cells, including genetic abnormalities. Disease progressions are mainly due to the inability of drugs to overcome refractory disease and inevitable drug-resistant relapse. In clinical practice, a bone marrow biopsy, mostly performed in one site, is still used to access the genetics of MM. However, BM biopsy use is limited by its invasive nature and by often not accurately reflecting the mutational profile of MM. Recent insights into the genetic landscape of MM provide a valuable opportunity to implement precision medicine approaches aiming to enable better patient profiling and selection of targeted therapies. In this review, we explore the use of the emerging field of liquid biopsies in myeloma patients considering current unmet medical needs, such as assessing the dynamic mutational landscape of myeloma, early predictors of treatment response, and a less invasive response monitoring.

摘要

多发性骨髓瘤(MM)是一种具有挑战性、进行性和高度异质性的血液恶性肿瘤。MM 的特征是骨髓(BM)中恶性浆细胞的多灶性增殖,有时也在骨髓外器官中。尽管有新的药物和更长的中位总生存期,但有些患者存活超过 10 年,而有些患者则迅速死亡。这种异质性主要是由 MM 细胞的生物学特性驱动的,包括遗传异常。疾病进展主要是由于药物无法克服难治性疾病和不可避免的耐药性复发。在临床实践中,骨髓活检(通常在一个部位进行)仍然用于评估 MM 的遗传学。然而,BM 活检的使用受到其侵袭性的限制,并且通常不能准确反映 MM 的突变特征。最近对 MM 遗传景观的深入了解为实施精准医学方法提供了宝贵的机会,旨在实现更好的患者分析和靶向治疗的选择。在这篇综述中,我们探讨了液体活检在骨髓瘤患者中的应用,考虑到目前未满足的医疗需求,如评估骨髓瘤的动态突变景观、治疗反应的早期预测因子以及侵袭性更小的反应监测。

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