From MGUS to multiple myeloma: Unraveling the unknown of precursor states

IF 6.9 2区 医学 Q1 HEMATOLOGY Blood Reviews Pub Date : 2024-11-01 DOI:10.1016/j.blre.2024.101242
Gil Hevroni , Mounika Vattigunta , Dickran Kazandjian , David Coffey , Benjamin Diamond , Francesco Maura , James Hoffman , Ola Landgren
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Abstract

In the 1960s, through laboratory-based investigations of peripheral blood partnered with detailed clinical annotations, Dr. Waldenström described a condition he called “benign monoclonal gammopathy”. These patients were asymptomatic with a detectable monoclonal protein, and did not meet imaging and laboratory criteria for multiple myeloma. In 1978, through observational retrospective review of medical records, Dr. Kyle observed that not all cases of monoclonal gammopathy were benign. He introduced the term monoclonal gammopathy of undetermined significance (MGUS) to describe a condition that may potentially progress to multiple myeloma (MM), highlighting clinical inability in predicting which patients might progress. In 1980, Drs. Kyle and Greipp described 6 cases which did not fit the definitions of MGUS or MM, and they remained asymptomatic after at least 5 years of follow-up; they were proposed to have smoldering multiple myeloma (SMM). Over time, SMM was defined by arbitrary numerical values (≥10 % plasma cells in the bone marrow and serum M-protein concentration ≥ 3 g/dL). Numerous clinical scores have been developed to define high-risk groups for progression to MM. Current statistical models for progression provide only average risk scores, offering limited clinical utility since the risk of progression at an individual level remains unknown. Physician-scientists are focusing on emerging technologies, such as whole genome sequencing, tumor microenvironment analysis, and single-cell RNA sequencing, to understand precursor states at a molecular level. The overarching goal of these technologies is to better characterize monoclonal gammopathy and other myeloma precursor states. This will enable clinicians to provide more precise, individualized risk assessments and ultimately improve patient outcomes. This review outlines the history of MM precursor states, current definitions, challenges in risk stratification models, and the role of emerging technologies in enhancing predictions and outcomes.
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从 MGUS 到多发性骨髓瘤:揭开前体状态的神秘面纱。
20 世纪 60 年代,通过对伴有详细临床注释的外周血进行实验室检查,瓦尔登斯特伦博士描述了一种他称之为 "良性单克隆性腺病 "的病症。这些患者没有症状,但可检测到单克隆蛋白,而且不符合多发性骨髓瘤的影像学和实验室标准。1978 年,凯尔博士通过对医疗记录的观察和回顾,发现并非所有的单克隆丙种球蛋白病都是良性的。他提出了 "意义未定的单克隆丙种球蛋白病"(MGUS)一词,用来描述一种有可能发展为多发性骨髓瘤(MM)的病症,强调临床上无法预测哪些患者可能会发展为多发性骨髓瘤。1980 年,Kyle 和 Greipp 医生描述了 6 例不符合 MGUS 或 MM 定义的病例,这些病例在随访至少 5 年后仍无症状;他们被认为患有烟雾型多发性骨髓瘤(SMM)。随着时间的推移,SMM 被任意用数值来定义(骨髓中浆细胞≥10%,血清 M 蛋白浓度≥3 g/dL)。目前已开发出许多临床评分方法,用于定义进展为 MM 的高危人群。目前的进展统计模型仅提供平均风险评分,临床实用性有限,因为个体水平的进展风险仍然未知。医生科学家们正在关注新兴技术,如全基因组测序、肿瘤微环境分析和单细胞 RNA 测序,以了解分子水平的前体状态。这些技术的总体目标是更好地描述单克隆丙种球蛋白病和其他骨髓瘤前体状态。这将使临床医生能够提供更精确、更个性化的风险评估,并最终改善患者的预后。本综述概述了骨髓瘤前体状态的历史、当前的定义、风险分层模型面临的挑战以及新兴技术在提高预测和预后方面的作用。
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来源期刊
Blood Reviews
Blood Reviews 医学-血液学
CiteScore
13.80
自引率
1.40%
发文量
78
期刊介绍: Blood Reviews, a highly regarded international journal, serves as a vital information hub, offering comprehensive evaluations of clinical practices and research insights from esteemed experts. Specially commissioned, peer-reviewed articles authored by leading researchers and practitioners ensure extensive global coverage across all sub-specialties of hematology.
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