UC Irvine

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.