1 磷酸鞘氨醇受体 1 (S1PR1) 的表达维持急性髓系白血病干细胞的干性。
Sphingosine-1 phosphate receptor 1 (S1PR1) expression maintains stemness of acute myeloid leukemia stem cells.
发表日期：2024 Aug 05
作者：
Yu-Qing Wang, Yue Ren, Robert Peter Gale, Li-Ting Niu, Xiao-Jun Huang
来源：
CANCER LETTERS
摘要：
急性髓系白血病 (AML) 起源于白血病干细胞 (LSC)，并由具有干性特征的细胞维持。我们比较了具有/不具有干细胞特征（定义为体外克隆性和免疫缺陷小鼠异种移植模型中的连续植入）的 AML 细胞的转录谱。我们使用多参数流式细胞术 (MPFC) 将 CD34 骨髓来源的白血病细胞分离为鞘氨醇-1 磷酸受体 1 (S1PR1) 和 S1PR1- 部分。与S1PR1-级分中的细胞相比，S1PR1级分中的细胞表现出显着更高的克隆形成性和更高的植入潜力。相反，与S1PR1-级分相比，来自正常样本的CD34+骨髓细胞在S1PR1级分中显示出克隆形成性降低。抑制 AML 细胞系中的 S1PR1 表达会降低 KG1 细胞的集落形成潜力。转录组分析和拯救实验表明 PI3K/AKT 通路和 MYBL2 是 S1PR1 相关干性的下游介质。这些发现表明 S1PR1 作为 LSC 的功能生物标志物，并表明其作为 AML 治疗靶点的潜力。版权所有 © 2024。由 Elsevier B.V. 出版。
Acute myeloid leukemia (AML) arises from leukemia stem cells (LSCs) and is maintained by cells which have acquired features of stemness. We compared transcription profiles of AML cells with/without stem cell features defined as in vitro clonogenicity and serial engraftment in immune-deficient mice xenograft model. We used multi-parameter flow cytometry (MPFC) to separate CD34+ bone marrow-derived leukemia cells into sphingosine-1 phosphate receptor 1 (S1PR1)+ and S1PR1- fractions. Cells in the S1PR1+ fraction demonstrated significantly higher clonogenicity and higher engraftment potential compared with those in the S1PR1- fraction. In contrast, CD34+ bone marrow cells from normal samples showed reduced clonogenicity in the S1PR1+ fraction compared with the S1PR1- fraction. Inhibition of S1PR1 expression in an AML cell line reduced the colony-forming potential of KG1 cells. Transcriptomic analyses and rescue experiments indicated PI3K/AKT pathway and MYBL2 are downstream mediators of S1PR1-associated stemness. These findings implicate S1PR1 as a functional biomarker of LSCs and suggest its potential as a therapeutic target in AML treatment.Copyright © 2024. Published by Elsevier B.V.