文章：

利用t分布随机邻域嵌入（t-SNE）方案对急性髓系白血病（AML）和骨髓增生异常综合征（MDS）患者CD34+细胞的表征研究

Characterization of CD34+Cells from Patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Using a t-Distributed Stochastic Neighbor Embedding (t-SNE) Protocol

原文发布日期：28 March 2024

DOI: 10.3390/cancers16071320

类型: Article

开放获取: 是

英文摘要：

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic cells from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to obtain deeper insight and segregation between leukemic cells and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34+/CD38−hematopoietic stem cells (HSCs) or CD34+cells with a strong co-expression of CD45RA/CD123, respectively. CD34+cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

摘要翻译： 

通过多色流式细胞术分析，我们研究了急性髓系白血病/骨髓增生异常综合征（AML/MDS）患者白血病细胞与治疗成功后完全缓解（CR）患者造血干细胞和祖细胞（HSPCs）之间的免疫表型差异。标记物组合包括代表层级性造血干细胞和祖细胞（HSPC）分类的CD34、CD38、CD45RA、CD123以及程序性死亡配体1（PD-L1）。我们未局限于二维或三维分析，而是应用t分布随机邻域嵌入（t-SNE）方法，以更深入地洞察并区分白血病细胞与正常HSPCs。为此，我们构建了t-SNE图谱，根据抗原表达组成和强度的相似性可视化呈现了27个细胞簇。其中两个簇为“白血病相关”，分别包含高比例的CD34+/CD38−造血干细胞（HSCs）或强共表达CD45RA/CD123的CD34+细胞。后一簇中的CD34+细胞亦高表达PD-L1，反映了其免疫抑制能力。除本原理验证研究外，纳入更多标记物将有助于细化正常HSPCs与白血病细胞的区分，尤其在微小残留病检测和抗原靶向治疗干预背景下。此外，我们提出一种基于t-SNE模式与参考图谱相似性比较、通过皮尔逊系数数值定量分配新细胞群的方案。

原文链接：

Characterization of CD34+Cells from Patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Using a t-Distributed Stochastic Neighbor Embedding (t-SNE) Protocol