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Hunting down the dominating subclone of cancer stem cells as a potential new therapeutic target in multiple myeloma: An artificial intelligence perspective
Authors:Lisa X Lee  Shengwen Calvin Li
Affiliation:Lisa X Lee, Division of Hematology/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, UCI Health, Orange, CA 92868, United StatesShengwen Calvin Li, Neuro-oncology and Stem Cell Research Laboratory, CHOC Children's Research Institute, Children's Hospital of Orange County, Orange, CA 92868, United StatesShengwen Calvin Li, Department of Neurology, University of California-Irvine School of Medicine, Orange, CA 92868, United States
Abstract:The development of single-cell subclones, which can rapidly switch from dormant to dominant subclones, occur in the natural pathophysiology of multiple myeloma(MM) but is often pressed by the standard treatment of MM. These emerging subclones present a challenge, providing reservoirs for chemoresistant mutations. Technological advancement is required to track MM subclonal changes, as understanding MM's mechanism of evolution at the cellular level can prompt the development of new targeted ways of treating this disease. Current methods to study the evolution of subclones in MM rely on technologies capable of phenotypically and genotypically characterizing plasma cells, which include immunohistochemistry, flow cytometry, or cytogenetics. Still, all of these technologies may be limited by the sensitivity for picking up rare events. In contrast, more incisive methods such as RNA sequencing, comparative genomic hybridization, or whole-genome sequencing are not yet commonly used in clinical practice. Here we introduce the epidemiological diagnosis and prognosis of MM and review current methods for evaluating MM subclone evolution, such as minimal residual disease/multiparametric flow cytometry/next-generation sequencing, and their respective advantages and disadvantages. In addition, we propose our new single-cell method of evaluation to understand MM's mechanism of evolution at the molecular and cellular level and to prompt the development of new targeted ways of treating this disease, which has a broad prospect.
Keywords:Multiple myeloma   Single cells   Single-cell transcriptome   Subclonal evolution   Cancer stem cells   Systemic tracking of single-cell landscape   Artificial intelligence medicine
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