Abstract：
With the advent of outperforming and massive laboratory tools, such as multiparameter flow cytometry and next-generation sequencing, hematopoietic cell clones with putative abnormalities for a variety of blood malignancies have been appreciated in otherwise healthy individuals. These conditions do not fulfill the criteria of their presumed cancer counterparts, and thus have been recognized as their precursor states. This is the case of monoclonal gammopathy of unknown significance (MGUS), the first blood premalignancy state described, preceding multiple myeloma (MM) or Waldenström macroglobulinemia (WM). However, in the last 2 decades, an increasing list of clonopathies has been recognized, including monoclonal B cell lymphocytosis (MBL), which antecedes chronic lymphocytic leukemia (CLL), clonal hematopoiesis of indeterminate potential (CHIP) for myeloid neoplasms (MN), and T-cell clones of uncertain significance (TCUS) for T-cell large chronic lymphocytic leukemia (LGLL). While for some of these entities diagnostic boundaries are precisely set, for others these are yet to be fully defined. Moreover, despite mostly considered of \"uncertain significance,\" they have not only appeared to predispose to malignancy, but also to be capable of provoking set of immunological and cardiovascular complications that may require specialized management. The clinical implications of the aberrant clones, together with the extensive knowledge generated on the pathogenetic events driving their evolution, raises the question whether earlier interventions may alter the natural history of the disease. Herein, we review this Tower of Babel of acronyms pinpointing diagnostic definitions, differential diagnosis, and the role of genomic profiling of these precursor states, as well as potential interventional strategies.
摘要：
随着优秀的大型实验室工具的出现，如多参数流式细胞术和下一代测序，在其他方面健康的个体中，具有各种血液恶性肿瘤推定异常的造血细胞克隆受到了赞赏。这些条件不符合其假定的癌症对应物的标准，因此被认为是他们的先驱状态。这是未知意义的单克隆丙种球蛋白病（MGUS），描述的第一个血液恶性前状态，在多发性骨髓瘤（MM）或Waldenström巨球蛋白血症（WM）之前。然而,在过去的20年里，越来越多的克隆病已经被发现，包括单克隆B细胞淋巴细胞增多症（MBL），在慢性淋巴细胞白血病（CLL）之前，髓系肿瘤（MN）的不确定潜能（CHIP）的克隆造血，T细胞大慢性淋巴细胞白血病（LGLL）的意义不确定的T细胞克隆（TCUS）。虽然对于这些实体中的一些，诊断边界是精确设定的，对于其他人来说，这些还没有完全定义。此外，尽管主要考虑到“不确定的意义”，“他们不仅似乎易患恶性肿瘤，但也能够引发一系列可能需要专门管理的免疫和心血管并发症。异常克隆的临床意义，加上对推动其进化的致病事件产生的广泛知识，提出了一个问题，即早期干预是否可能改变疾病的自然史。在这里，我们回顾这个通天塔的首字母缩略词，指出诊断定义，鉴别诊断,以及这些前体状态的基因组图谱的作用，以及潜在的干预策略。
