慢性淋巴细胞性白血病患有两个B细胞的单个患者不一致的轻链限制：双隆B细胞肿瘤的平行发展或同型开关的克隆进化？
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?
影响因子:1.90000
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
摘要
为了评估双隆慢性淋巴细胞性白血病（CLL）的临床病理特征。反应地分析临床数据和病理学特征。鉴定出流式细胞仪表现出异常的B细胞量，表现出具有CLL样免疫型的异常B细胞种群，但显示出明确的轻型光链限制性。所有这些都检测到了细胞遗传学异常，其中包括七个与CLL相关的异常。其中四个显示了暗示克隆进化的特征，所有特征都具有DEL（13Q）为“词干线”异常，三个以“侧线”异常表示DEL（11Q）。在对照组的单克隆CLL组中，有5例（50％）病例显示出有害的Notch1突变（P <.05）。在10例患者中，有5例接受治疗，在三例病例中有良好/部分反应，在一个情况下进行治疗性抗性。估计无治疗的中位生存期为68个月。尽管有一多型光链表达的模式，但通过特征性的CLL表型提出了双隆声CLL的肿瘤性质，并且可以通过细胞遗传学和基因组分析来证实。具有不一致的轻链同型的两个克隆可能具有“茎线”的细胞遗传学异常，表明可能的克隆进化。双隆CLL与Notch1突变有关，该突变可能发生在小亚克隆中，并逐渐发展为克隆大小。对轻链排序和/或按时间顺序收集的样品进行基因组分析可能会洞悉CLL克隆进化。
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.