Gong Lixin, Qiu Lugui, Hao Mu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Road, Tianjin 300020, China.
Tianjin Institutes of Health Science, Tianjin 300020, China.
Cancers (Basel). 2024 Jan 24;16(3):498. doi: 10.3390/cancers16030498.
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（MM）的进化史包括恶性转化，随后进展为癌前阶段和明显的恶性肿瘤，最终导致更具侵袭性和耐药性的形式。在过去十年中，人们付出了巨大努力来确定MM中的潜在治疗靶点。然而，MM在很大程度上仍然无法治愈。大多数患者经历多次复发，最终不可避免地对治疗产生耐药性。肿瘤起始细胞群体被认为是导致许多血液系统恶性肿瘤复发的原因。随着MM疾病的进展，已经发现了肿瘤细胞的克隆进化。由于异质性MM细胞克隆对治疗的反应不同，更具侵袭性的群体存活并进化。此外，肿瘤微环境是一个复杂的生态系统，在支持肿瘤细胞进化方面发挥着多方面的作用。新兴的单细胞分辨率多组学研究允许对肿瘤细胞和微环境进行综合和全面的分析，加深了对MM生物学特征的理解。在这篇综述中，我们打算讨论新兴的多组学研究所揭示的关于MM中肿瘤细胞起始、克隆进化、耐药性和肿瘤微环境的新见解。这些数据提出了一种有前景的策略，以揭示MM进展的关键机制，并实现整体和精确的治疗改善。
