The evolutionary history of multiple myeloma (MM) includes malignant transformation, followed by progression to pre-malignant stages and overt malignancy, ultimately leading to more aggressive and resistant forms. Over the past decade, large effort has been made to identify the potential therapeutic targets in MM. However, MM remains largely incurable. Most patients experience multiple relapses and inevitably become refractory to treatment. Tumor-initiating cell populations are the postulated population, leading to the recurrent relapses in many hematological malignancies. Clonal evolution of tumor cells in MM has been identified along with the disease progression. As a consequence of different responses to the treatment of heterogeneous MM cell clones, the more aggressive populations survive and evolve. In addition, the tumor microenvironment is a complex ecosystem which plays multifaceted roles in supporting tumor cell evolution. Emerging multi-omics research at single-cell resolution permits an integrative and comprehensive profiling of the tumor cells and microenvironment, deepening the understanding of biological features of MM. In this review, we intend to discuss the novel insights into tumor cell initiation, clonal evolution, drug resistance, and tumor microenvironment in MM, as revealed by emerging multi-omics investigations. These data suggest a promising strategy to unravel the pivotal mechanisms of MM progression and enable the improvement in treatment, both holistically and precisely.
多发性骨髓瘤的演化历程包括恶性转化、向癌前阶段及显性恶性肿瘤进展，最终发展为更具侵袭性和耐药性的形式。过去十年间，学界在识别多发性骨髓瘤潜在治疗靶点方面投入巨大努力，但该疾病目前仍基本无法治愈。多数患者经历多次复发，最终不可避免地产生治疗耐药性。肿瘤起始细胞群被认为是导致多种血液恶性肿瘤反复复发的假定细胞群体。研究已证实多发性骨髓瘤肿瘤细胞随疾病进展发生克隆演化，由于异质性骨髓瘤细胞克隆对治疗产生差异化反应，更具侵袭性的细胞群体得以存活并进化。此外，肿瘤微环境作为复杂的生态系统，在支持肿瘤细胞演化过程中发挥多层面作用。新兴的单细胞分辨率多组学研究实现了对肿瘤细胞及其微环境的整合性全面解析，深化了对多发性骨髓瘤生物学特征的理解。本综述旨在探讨通过新兴多组学研究揭示的关于多发性骨髓瘤肿瘤细胞起始、克隆演化、耐药机制及肿瘤微环境的新见解。这些数据为系统而精准地揭示多发性骨髓瘤进展的关键机制、推动治疗策略改进提供了前景广阔的研究路径。
肿瘤(癌症)患者之家