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.

BACKGROUND T-cell large granular lymphocytic leukemia (T-LGL) is a rare hematological malignancy that currently has no standard therapy. Immunoglobulin heavy chain amyloidosis (AH) involving the kidney is a rare condition and the pathology, diagnosis, clinical characteristics, and prognosis are becoming understood. This report is of a rare case of T-LGL associated with renal AH and discusses the approach to management. CASE REPORT A 57-year-old woman presented with symptoms of fatigue and she had proteinuria. A diagnosis of T-LGL associated with renal AH was made, which is an association that has not been previously reported in the literature. Given the dysregulation of her immune function due to her underlying T-LGL and her comorbidities, treatment options were limited. She was clinically stable and was initially observed. After one year, her symptoms of fatigue became worse, and her proteinuria increased. Treatment was initiated with the triple drug combination of bortezomib, cyclophosphamide, and dexamethasone (CyBorD) with consideration for future hematopoietic stem cell transplantation (HSCT). Her clinical condition improved, with a reduction in proteinuria. CONCLUSIONS A rare case of T-LGL and renal AH is presented. Currently, there is no standard therapy for T-LGL and AH amyloidosis, and the approach, in this case, was to manage the patient initially with CyBorD triple chemotherapy.