患者个体中两种不同轻链约束的B细胞群体的慢性淋巴细胞白血病。
Chronic Lymphocytic Leukemia With Two B-Cell Populations of Discordant Light Chain Restrictions in Individual Patients.
发表日期：2023 Feb 07
作者：
Yue Zhao, Imran Siddiqi, Tyler J Wildes, Jenna McCracken, Kristen Deak, Catherine Rehder, Endi Wang
来源：
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
摘要：
评估双克隆型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。共鉴定了十例病例，流式细胞术显示异常的B细胞群体，具有类似CLL的免疫表型但没有明确的轻链限制。所有人均检测到细胞遗传学异常，其中包括七例存在两种与CLL有关的异常。其中四例表现出克隆演化的特征，所有这些病例的"干细胞系"异常都是del(13q)，而其中三例显示del(11q)为"副细胞系"异常。五（50％）例呈现出有害的NOTCH1基因突变，相比单克隆型CLL的对照组的11.8％，明显增加（P < .05）。在十名患者中，5名接受了治疗，其中三例有良好/部分反应，一例治疗抵抗。中位无治疗生存期估计为68个月。尽管具有多类型轻链表达模式，但双克隆型CLL的肿瘤性质可由CLL表型和细胞遗传和基因组分析证实。与不同轻链异型的两个克隆可能共享一个“干细胞系”细胞遗传学异常，从而暗示可能有克隆演化。双克隆型CLL与NOTCH1基因突变相关，这可能发生在一个小的亚克隆中，并逐渐演化成克隆大小。在轻链分选和/或时间上收集的样本中进行基因组分析可以为CLL的克隆演变提供见解。© 作者（2023）。由牛津大学出版社代表美国临床病理学会出版。保留所有权利。请发送电子邮件至journals.permissions@oup.com以获取许可权限。
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.© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.