Salomon-Perzyński Aleksander, Jamroziak Krzysztof, Głodkowska-Mrówka Eliza
Department of Hematology, Institute of Hematology and Transfusion Medicine, 14 I. Gandhi St., 02-776 Warsaw, Poland.
Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 1A Banach St., 02-097 Warsaw, Poland.
Diagnostics (Basel). 2021 Aug 25;11(9):1534. doi: 10.3390/diagnostics11091534.
Plasma cell dyscrasias are a heterogeneous group of diseases characterized by the expansion of bone marrow plasma cells. Malignant transformation of plasma cells depends on the continuity of events resulting in a sequence of well-defined disease stages, from monoclonal gammopathy of undetermined significance (MGUS) through smoldering myeloma (SMM) to symptomatic multiple myeloma (MM). Evolution of a pre-malignant cell into a malignant cell, as well as further tumor progression, dissemination, and relapse, require development of multiple driver lesions conferring selective advantage of the dominant clone and allowing subsequent evolution under selective pressure of microenvironment and treatment. This process of natural selection facilitates tumor plasticity leading to the formation of genetically complex and heterogenous tumors that are notoriously difficult to treat. Better understanding of the mechanisms underlying tumor evolution in MM and identification of lesions driving the evolution from the premalignant clone is therefore a key to development of effective treatment and long-term disease control. Here, we review recent advances in clonal evolution patterns and genomic landscape dynamics of MM, focusing on their clinical implications.
浆细胞异常增殖性疾病是一组异质性疾病，其特征为骨髓浆细胞扩增。浆细胞的恶性转化取决于一系列事件的连续性，这些事件导致了一系列明确的疾病阶段，从不明意义的单克隆丙种球蛋白病（MGUS）到冒烟型骨髓瘤（SMM），再到有症状的多发性骨髓瘤（MM）。癌前细胞向恶性细胞的演变，以及进一步的肿瘤进展、播散和复发，需要多个驱动性病变的发展，这些病变赋予优势克隆选择性优势，并使其在微环境和治疗的选择性压力下得以后续演变。这种自然选择过程促进了肿瘤可塑性，导致形成基因复杂且异质性的肿瘤，而这些肿瘤 notoriously 难以治疗。因此，更好地理解 MM 肿瘤演变的潜在机制，并识别驱动癌前克隆演变的病变，是开发有效治疗方法和实现长期疾病控制的关键。在此，我们综述 MM 克隆进化模式和基因组格局动态的最新进展，重点关注其临床意义。
