具有两种不匹配轻链限制的双克隆B细胞群的慢性淋巴细胞白血病：双克隆B细胞肿瘤的平行发展还是同源克隆的免疫球蛋白变异？
Chronic Lymphocytic Leukemia With Two B-Cell Populations of Discordant Light Chain Restrictions in Individual Patients: Parallel Development of Biclonal B-Cell Neoplasms or Clonal Evolution With Isotype Switch?
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影响因子:1.9
分区:医学4区 / 病理学3区
发表日期:2023 Apr 04
作者:
Yue Zhao, Imran Siddiqi, Tyler J Wildes, Jenna McCracken, Kristen Deak, Catherine Rehder, Endi Wang
DOI:
10.1093/ajcp/aqac165
摘要
本研究旨在评估双克隆慢性淋巴细胞白血病（CLL）的临床病理特征。回顾性分析临床数据和病理特征。共识别出10例流式细胞术显示具有异常B细胞群，但表现为CLL样免疫表型且无明确轻链限制的病例。所有病例均检测到染色体异常，包括7例具有两个与CLL相关的异常。这些病例中有4例表现出克隆进化的特征，所有这些都具有del(13q)作为“干线”异常，3例具有del(11q)作为“侧线”异常。5例（50%）显示有有害的NOTCH1突变，而对照组单克隆CLL中这一比例为11.8%（P < 0.05）。在10例患者中，有5例接受了治疗，其中3例获得良好/部分反应，1例出现治疗抵抗。中位无治疗存活期估计为68个月。尽管表现出多型性轻链表达，但双克隆CLL的肿瘤性质由其特征性的CLL表型所提示，并可通过细胞遗传学和基因组学分析确认。两种具有不匹配轻链类型的克隆可能共享“干线”染色体异常，提示可能存在克隆进化。双克隆CLL与NOTCH1突变相关，这些突变可能在小的亚克隆中发生，并逐渐在克隆大小上演变。对轻链分选和/或按时间收集的样本进行基因组分析，可能有助于揭示CLL中的克隆进化过程。
Abstract
To evaluate clinicopathologic characteristics of biclonal chronic lymphocytic leukemia (CLL).Retrospectively analyze clinical data and pathologic features.Ten cases were identified in which flow cytometry demonstrated an abnormal B-cell population with a CLL-like immunophenotype but showed no definitive light chain restriction. All had cytogenetic abnormalities detected, including seven with two CLL-related abnormalities. Four of these showed features suggestive of clonal evolution, all having del(13q) as a "stem-line" abnormality and three showing del(11q) as a "side-line" abnormality. Five (50%) cases demonstrated deleterious NOTCH1 mutations, in contrast to 11.8% in a control group of monoclonal CLL (P < .05). Of the 10 patients, 5 received treatment, with good/partial response in three cases and therapeutic resistance in one case. The median treatment-free survival was estimated at 68 months.Despite a polytypic pattern of light chain expression, the neoplastic nature of biclonal CLL is suggested by a characteristic CLL phenotype and can be confirmed by cytogenetic and genomic analyses. The two clones with discordant light chain isotypes may share a "stem-line" cytogenetic abnormality, suggesting possible clonal evolution. Biclonal CLL is associated with NOTCH1 mutations, which may occur in a small subclone and gradually evolve in clonal size. Genomic analysis on light chain-sorted and/or chronologically collected samples may provide insight into clonal evolution in CLL.