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.
Keyphrases
- stem cells
- acute myeloid leukemia
- induced apoptosis
- bone marrow
- cell cycle arrest
- allogeneic hematopoietic stem cell transplantation
- epithelial mesenchymal transition
- mesenchymal stem cells
- endoplasmic reticulum stress
- flow cytometry
- signaling pathway
- cell death
- risk assessment
- computed tomography
- binding protein
- cell therapy
- rna seq