Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
Blood Cancer J. 2024 Nov 6;14(1):193. doi: 10.1038/s41408-024-01175-8.
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）的前驱状态，其特征是血液中存在单克隆 B 细胞。镶嵌染色体改变（mCAs）是一种克隆性造血形式，包括大片段 DNA 的获得、缺失和非等位基因丢失。MBL 和 mCAs 均已被发现会增加 CLL 和淋巴恶性肿瘤的风险，而我们的研究目的是调查 mCAs 与目前未知的 MBL 之间的关系。我们分析了来自梅奥诊所生物库和 CLL 数据库的 4632 名个体的遗传、流式细胞术和血液学数据。MBL 是通过流式细胞术检测的，并根据克隆大小分为高计数（HC）或低计数（LC）MBL。mCAs 主要通过全血 DNA 进行 SNP 芯片分析检测。在 MBL 和 CLL 中常见改变的 mCAs（6q、11q、13q、17p 缺失和 12 号三体）特异性（>99%）高，仅存在于 MBL 和 CLL 个体中。HC-MBL 和 LC-MBL 个体分别有 881 倍和 8 倍更可能携带 CLL 相关 mCAs，而没有 MBL 的个体则没有。这些 mCAs 所在的细胞群通常超过 B 细胞群，这表明它们起源于 B 细胞系之前。整合遗传和血液计数数据可以在生物库样本中以高特异性检测到 HC-MBL。这些结果量化了 mCAs 对 MBL 的贡献，并可以在无需流式细胞术筛选的情况下对 HC-MBL 进行大型研究。
