DataSheet_1_Differential diagnosis and identification of prognostic markers for peripheral T-cell lymphoma subtypes based on flow cytometry immunophenotype profiles.docx

We compared the differential expression of 15 markers in PTCL (Peripheral T-cell lymphoma) subtypes and T-CUS (T-cell clones of uncertain significance), and summarized the specific immunophenotype profiles of each subtype and its impact on prognosis. PD-1 and CD10 are diagnostic markers for AITL (angioimmunoblastic T-cell lymphoma). To avoid confusion with T-CUS of benign clones, it is recommended to define AITL as bounded by PD-1+%>38.01 and/or CD10+%>7.46. T cell-derived ENKTL-N (extranodal NKT cell lymphoma) specifically expresses CD56. ALCL (anaplastic large cell lymphoma) characteristically expresses CD30 and HLA-DR. PTCL-NOS (peripheral T-cell lymphoma unspecified) still lacks a relatively specific phenotype and is prone to loss of basic lineage markers CD3, CD5, and CD7. The determination of T-CUS can be verified by the overall assessment of the bone marrow and a certain period of follow-up. The clustering results showed that the expression of 8 specific markers was significantly different among the 5 groups, suggesting that a combination of related markers can be analyzed in the identification of PTCLs subtypes. The study explores the advantages of TRBC1 combined with CD45RA/CD45RO in detecting T cell clonality, which can efficiently and sensitively analyze multiple target T cell populations at the same time. The sensitivity of PB to replace BM to monitor the tumor burden or MRD (minimal residual disease) of PTCLs is as high as 85.71%, which can relieve the huge pressure of clinical sampling and improve patient compliance. CD7, CD38, and Ki-67 are prognostic indicators for AITL. CD3 and CD8 on PTCL-NOS, and CD56 and HLA-DR on ENKTL-N have prognostic role. This study supports and validates the current classification of PTCL subtypes and establishes an immunophenotypic profile that can be used for precise diagnosis. The important clinical value of PTCLs immunophenotype in routine classification diagnosis, clonality confirmation, prognosis prediction, and treatment target selection was emphasized.

本研究对比了15种标志物在**外周T细胞淋巴瘤（Peripheral T-cell lymphoma, PTCL）**亚型及**意义未明T细胞克隆（T-cell clones of uncertain significance, T-CUS）**中的差异表达情况，并总结了各亚型的特异性免疫表型特征及其对预后的影响。PD-1与CD10是**血管免疫母细胞性T细胞淋巴瘤（angioimmunoblastic T-cell lymphoma, AITL）**的诊断标志物。为避免与良性克隆性T-CUS混淆，建议以PD-1阳性率>38.01%及/或CD10阳性率>7.46%作为AITL的界定标准。T细胞来源的**结外NKT细胞淋巴瘤（extranodal NKT cell lymphoma, ENKTL-N）**特异性表达CD56。**间变性大细胞淋巴瘤（anaplastic large cell lymphoma, ALCL）**特征性表达CD30与HLA-DR。**非特指型外周T细胞淋巴瘤（peripheral T-cell lymphoma unspecified, PTCL-NOS）**目前仍缺乏相对特异性的表型，且易丢失T细胞谱系基本标志物CD3、CD5与CD7。T-CUS的确诊可通过骨髓全面评估及一定周期的随访来验证。聚类分析结果显示，5组样本间8种特异性标志物的表达存在显著差异，提示可通过联合检测相关标志物来辅助PTCL亚型的鉴别诊断。本研究探讨了TRBC1联合CD45RA/CD45RO检测T细胞克隆性的优势，该方案可同时高效、灵敏地分析多种目标T细胞群体。以**外周血（Peripheral Blood, PB）**替代**骨髓（Bone Marrow, BM）**监测PTCL肿瘤负荷或**微小残留病（minimal residual disease, MRD）**的灵敏度高达85.71%，可大幅缓解临床采样压力并提升患者依从性。CD7、CD38与Ki-67是AITL的预后标志物。PTCL-NOS的CD3、CD8以及ENKTL-N的CD56与HLA-DR同样具有预后价值。本研究支持并验证了当前PTCL亚型分类体系，并建立了可用于精准诊断的免疫表型特征谱。本研究强调了PTCL免疫表型在常规分类诊断、克隆性确认、预后预测及治疗靶点选择中的重要临床价值。