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. 2024 Sep 28:600:217158.
doi: 10.1016/j.canlet.2024.217158. Epub 2024 Aug 5.

Sphingosine-1 phosphate receptor 1 (S1PR1) expression maintains stemness of acute myeloid leukemia stem cells

Yu-Qing Wang  1 , Yue Ren  2 , Robert Peter Gale  3 , Li-Ting Niu  2 , Xiao-Jun Huang  4
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Free article

Sphingosine-1 phosphate receptor 1 (S1PR1) expression maintains stemness of acute myeloid leukemia stem cells

Yu-Qing Wang et al. Cancer Lett. .
Free article

Abstract

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.

Keywords: Acute myeloid leukemia; Leukemia stem cells; S1PR1.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Peter Gale reports a relationship with Antengene Biotech Limited Liability Company that includes: consulting or advisory. Robert Peter Gale reports a relationship with FFF Enterprises Inc that includes: board membership. Robert Peter Gale reports a relationship with Janssen Pharma and Hengrui Pharma that includes: speaking and lecture fees. Robert Peter Gale reports a relationship with Russian Foundation for Cancer Research Support and Scientific Advisory Board, StemRad Ltd that includes: board membership. Xiaojun Huang has patent #202310435300.1 pending to Peking University People's Hospital. Xiaojun Huang has patent #202311626667.8 pending to Peking University People's Hospital. No If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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