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.

MBL 是慢性淋巴细胞白血病 （CLL） 的前体疾病，其特征是血液中存在单克隆 B 细胞。嵌方染色体改变 （mCA） 是克隆造血的一种形式，包括大 DNA 片段的获得、丢失和拷贝中性杂合性丢失。已发现 MBL 和 mCAs 都会增加 CLL 和淋巴恶性肿瘤的风险，我们研究的目的是调查 mCA 与 MBL 的关系，目前尚不清楚。我们分析了来自梅奥诊所生物样本库和 CLL 数据库的 4632 名个体的遗传、流式细胞术和血液学数据。使用流式细胞术检测 MBL，并根据克隆大小分为高计数 （HC） 或低计数 （LC） MBL。使用基于敏感的 SNP 阵列分析，主要从全血 DNA 中检测 mCA。CLL 中常见改变的 mCAs （6q 、 11q 、 13q 、 17p 和 12 三体缺失） 对 MBL 和 CLL 个体具有特异性 （>99%）。HC-MBL 和 LC-MBL 个体携带 CLL 相关 mCAs 的可能性分别是无 MBL 个体的 881 倍和 8 倍。携带这些 mCA 的细胞组分通常超过 B 细胞组分，表明它们起源于 B 细胞谱系。整合遗传和血细胞计数数据能够以高特异性检测生物样本库中的 HC-MBL。这些结果量化了 mCAs 对 MBL 的贡献，并且可以在不需要流式细胞术筛选的情况下进行 HC-MBL 的大规模研究。