MBL is a precursor condition to chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cells in blood. Mosaic chromosomal alterations (mCAs) are a form of clonal hematopoiesis that include gains, losses, and copy-neutral loss-of-heterozygosity of large DNA segments. Both MBL and mCAs have been found to increase the risk of CLL and lymphoid malignancies, and the aim of our study was to investigate how mCAs relate to MBL, which is currently unknown. We analyzed genetic, flow cytometric, and hematologic data from 4632 individuals from the Mayo Clinic Biobank and CLL Database. MBL was detected using flow cytometry and classified as high-count (HC) or low-count (LC) MBL based on clone size. mCAs were detected primarily from whole blood DNA using sensitive SNP-array-based analyses. mCAs commonly altered in CLL (deletion of 6q, 11q, 13q, 17p, and trisomy 12) were specific (>99%) to individuals with MBL and CLL. HC-MBL and LC-MBL individuals were 881-fold and 8-fold, respectively, more likely to harbor CLL-associated mCAs than those without MBL. The cell fraction bearing these mCAs typically exceeded the B-cell fraction, suggesting their origin prior to the B-cell lineage. Integrating genetic and blood count data enabled detecting HC-MBL with high specificity in a biobank sample. These results quantify the contribution of mCAs to MBL and could enable large studies of HC-MBL without the need for flow cytometric screening.
单克隆B淋巴细胞增多症（MBL）是慢性淋巴细胞白血病（CLL）的前期病变，其特征为血液中存在单克隆B细胞。嵌合染色体改变（mCAs）是克隆性造血的一种形式，涉及大片段DNA的获得、缺失及拷贝数中性杂合性缺失。研究发现MBL和mCAs均会增加CLL及淋巴系统恶性肿瘤的风险，而本研究旨在探究目前未知的mCAs与MBL之间的关联。我们分析了来自梅奥诊所生物样本库及CLL数据库的4632名个体的遗传学、流式细胞学和血液学数据。通过流式细胞术检测MBL，并根据克隆大小将其分为高计数型（HC）或低计数型（LC）MBL。主要通过基于高灵敏度SNP芯片分析的全血DNA检测mCAs。在CLL中常见的mCAs改变（6q、11q、13q、17p缺失及12号染色体三体）对MBL和CLL患者具有高度特异性（>99%）。与非MBL个体相比，HC-MBL和LC-MBL个体携带CLL相关mCAs的可能性分别高出881倍和8倍。携带这些mCAs的细胞比例通常超过B细胞比例，提示其起源早于B细胞谱系。整合遗传学与血细胞计数数据可在生物样本库样本中高特异性检测HC-MBL。这些结果量化了mCAs对MBL的影响，并为无需流式细胞术筛查即可开展大规模HC-MBL研究提供了可能。
Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL)
肿瘤(癌症)患者之家