Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL)

IF 12.9 1区 医学 Q1 HEMATOLOGY Blood Cancer Journal Pub Date : 2024-11-06 DOI:10.1038/s41408-024-01175-8
Aswin Sekar, Rosalie Griffin, Sameer A. Parikh, Giulio Genovese, Dennis P. Robinson, Aaron D. Norman, Janet E. Olson, Kari G. Rabe, Mingma S. Hoel, Nicholas J. Boddicker, Paul J. Hampel, Neil E. Kay, James R. Cerhan, Esteban Braggio, Curtis A. Hanson, Celine M. Vachon, Tait D. Shanafelt, Benjamin L. Ebert, Susan L. Slager
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Abstract

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.

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单克隆 B 细胞淋巴细胞增多症 (MBL) 患者的染色体镶嵌改变 (mCA)
MBL 是慢性淋巴细胞白血病(CLL)的前驱病症,其特征是血液中的单克隆 B 细胞。镶嵌染色体改变(mCAs)是克隆造血的一种形式,包括大DNA片段的增益、缺失和拷贝中性杂合子丢失。研究发现,MBL 和 mCAs 都会增加罹患 CLL 和淋巴恶性肿瘤的风险。我们分析了梅奥诊所生物库和 CLL 数据库中 4632 人的遗传学、流式细胞术和血液学数据。使用流式细胞仪检测 MBL,并根据克隆大小将其分为高计数(HC)和低计数(LC)MBL。mCAs 主要通过基于敏感 SNP 阵列的分析从全血 DNA 中检测。与没有 MBL 的人相比,HC-MBL 和 LC-MBL 人携带 CLL 相关 mCA 的可能性分别高 881 倍和 8 倍。携带这些 mCAs 的细胞部分通常超过 B 细胞部分,这表明它们起源于 B 细胞系之前。通过整合基因和血细胞计数数据,可以在生物库样本中检测到高特异性的 HC-MBL。这些结果量化了 mCA 对 MBL 的贡献,无需流式细胞筛选就能对 HC-MBL 进行大规模研究。
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来源期刊
CiteScore
16.70
自引率
2.30%
发文量
153
审稿时长
>12 weeks
期刊介绍: Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as: Preclinical studies of new compounds, especially those that provide mechanistic insights Clinical trials and observations Reviews related to new drugs and current management of hematologic malignancies Novel observations related to new mutations, molecular pathways, and tumor genomics Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.
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