Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Blood. 2011 Oct 20;118(16):4384-93. doi: 10.1182/blood-2011-02-338517. Epub 2011 Aug 24.
T-cell large granular lymphocyte leukemia (T-LGLL) is characterized by chronic lymphoproliferation of cytotoxic T lymphocytes (CTLs) and is associated with lineage-restricted cytopenias. Introduction of T-cell receptor (TCR) variable β-chain (Vβ) monoclonal antibodies has facilitated identification and enumeration of clonal CTLs by flow cytometry. A highly skewed TCR Vβ repertoire identified by flow cytometry is strongly associated with monoclonal CDR3 regions by quantitative sequencing and positive TCRγ rearrangement assays. Therefore, Vβ expansions can serve as surrogate markers of CTL clonality to assess clonal kinetics in T-LGLL. We analyzed the TCR repertoire in 143 patients, 71 of which were available for serial measurements over 6 to 96 months. Although the majority (38/71, 54%) maintained a consistent monoclonal expansion, many (26/71, 37%) unexpectedly displayed a change in the dominant clone, whereby the original CTL clone contracted and another emerged as demonstrated by Vβ typing. Our results demonstrate that the T-cell repertoire is more dynamic in T-LGLL than recognized previously, illustrating the heterogeneity of disorders under this categorization.
T 细胞大颗粒淋巴细胞白血病（T-LGLL）的特征是细胞毒性 T 淋巴细胞（CTL）的慢性淋巴增殖，并伴有谱系受限的血细胞减少症。T 细胞受体（TCR）可变 β 链（Vβ）单克隆抗体的引入通过流式细胞术促进了克隆 CTL 的鉴定和计数。流式细胞术鉴定的高度偏倚 TCR Vβ 谱通过定量测序和阳性 TCRγ 重排分析与单克隆 CDR3 区域强烈相关。因此，Vβ 扩增可以作为 CTL 克隆性的替代标志物，以评估 T-LGLL 中的克隆动力学。我们分析了 143 例患者的 TCR 谱，其中 71 例可进行 6 至 96 个月的连续测量。尽管大多数（38/71，54%）保持一致的单克隆扩增，但许多（26/71，37%）出乎意料地显示出主导克隆的变化，原始 CTL 克隆收缩，另一个克隆出现，如 Vβ 分型所示。我们的结果表明，T-LGLL 中的 T 细胞谱比以前认识到的更具动态性，说明了该分类下疾病的异质性。
