Novel Insights into the Initiation, Evolution, and Progression of Multiple Myeloma by Multi-Omics Investigation
Lixin Gong1,2, Lugui Qiu1,2,3, Mu Hao1,2
1State 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.
Abstract:
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.
Insights
Multiple myeloma (MM) evolution involves clonal expansion and drug resistance, driven by tumor-initiating cells and the microenvironment. Advanced multi-omics research offers new therapeutic strategies for this incurable cancer.
Area of Science:
- Hematology
- Oncology
- Genomics
Background:
- Multiple myeloma (MM) is a largely incurable hematological malignancy characterized by malignant transformation, progression, and relapse.
- Despite therapeutic efforts, most patients develop treatment resistance due to clonal evolution and the tumor microenvironment.
- Tumor-initiating cells are implicated in the recurrent relapses observed in MM.
Purpose of the Study:
- To review novel insights into multiple myeloma (MM) progression, focusing on tumor cell initiation, clonal evolution, drug resistance, and the tumor microenvironment.
- To highlight the impact of emerging multi-omics research at single-cell resolution on understanding MM biology.
- To discuss how these advancements can inform improved and precise therapeutic strategies for MM.
Main Methods:
- Review of recent multi-omics investigations, particularly those employing single-cell resolution.
- Analysis of data pertaining to tumor cell heterogeneity, clonal dynamics, and drug resistance mechanisms in MM.
- Examination of the role of the tumor microenvironment in supporting MM progression.
Main Results:
- Multi-omics studies reveal complex clonal evolution patterns in MM, with aggressive clones surviving treatment.
- The tumor microenvironment significantly influences MM cell evolution and therapeutic resistance.
- Single-cell resolution enables comprehensive profiling of MM cells and their surrounding ecosystem.
Conclusions:
- Emerging multi-omics data provide critical insights into the pivotal mechanisms driving MM progression.
- Understanding tumor cell initiation, evolution, and microenvironment interactions is key to overcoming MM.
- These findings pave the way for developing more effective and personalized treatments for multiple myeloma.
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