Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.
Department of Hematology and Stem Cell Transplantation, South Pest Central Hospital-National Institute for Hematology and Infectious Diseases, Budapest, Hungary.
Geroscience. 2023 Apr;45(2):727-746. doi: 10.1007/s11357-022-00698-x. Epub 2022 Dec 12.
Multiple myeloma (MM) is an incurable plasma cell malignancy, which is predominantly a disease of older adults (the median age at diagnosis is 70 years). The slow progression from asymptomatic stages and the late-onset of MM suggest fundamental differences compared to many other hematopoietic system-related malignancies. The concept discussed in this review is that age-related changes at the level of terminally differentiated plasma cells act as the main risk factors for the development of MM. Epigenetic and genetic changes that characterize both MM development and normal aging are highlighted. The relationships between cellular aging processes, genetic mosaicism in plasma cells, and risk for MM and the stochastic processes contributing to clonal selection and expansion of mutated plasma cells are investigated. In line with the DNA damage accumulation theory of aging, in this review, the evolution of monoclonal gammopathy to symptomatic MM is considered. Therapeutic consequences of age-dependent comorbidities that lead to frailty and have fundamental influence on treatment outcome are described. The importance of considering geriatric states when planning the life-long treatment course of an elderly MM patient in order to achieve maximal therapeutic benefit is emphasized.
多发性骨髓瘤（MM）是一种无法治愈的浆细胞恶性肿瘤，主要发生在老年人（诊断时的中位年龄为 70 岁）。从无症状阶段的缓慢进展和 MM 的发病较晚可以看出，其与许多其他造血系统相关的恶性肿瘤存在根本差异。本综述中讨论的观点是，终末分化浆细胞水平的与年龄相关的变化是 MM 发展的主要危险因素。突出了既表征 MM 发生发展又表征正常衰老的表观遗传和遗传变化。研究了细胞衰老过程、浆细胞遗传镶嵌性与 MM 风险之间的关系，以及导致突变浆细胞克隆选择和扩增的随机过程。根据衰老的 DNA 损伤积累理论，本综述考虑了单克隆丙种球蛋白血症向有症状 MM 的演变。描述了与年龄相关的合并症导致虚弱并对治疗结果产生根本影响的治疗后果。强调在为老年 MM 患者制定终身治疗方案时考虑老年状态的重要性，以实现最大的治疗效益。
