Abstract:
Objective To investigate the mechanism of impact of bone marrow-derived mesenchymal stromal cells (BM-MSCs) on acute myeloid leukemia (AML) cells.
Methods An overexpressed MLL-AF9-induced AML mouse model was used, and the expression of thrombospondin-1 (TSP-1) was compared between BM-MSCs from AML and wild-type (WT) mice by PCR analysis. TSP-1-overexpressing BM-MSCs were co-cultured with primary AML cells following lentivirus transfection, and the growth of AML cells and expression of TSP-1 receptors (CD36 and CD47) on their surface was detected. The CD36 inhibitor N-oleoylthiosuccinimide was introduced to the co-culture system and AML cell proliferation and apoptosis were observed.
Results TSP-1 expression in BM-MSCs derived from AML mice was lower than that in WT mice. Flow cytometry results revealed that CD36 expression increased but CD47 expression remained unchanged in primary AML cells co-cultured with TSP-1-overexpressing BM-MSCs. Furthermore, AML cell growth was inhibited following co-culturing with TSP-1-overexpressing BM-MSCs. The addition of N-oleoylthiosuccinimide increased AML cell proliferation while inhibiting apoptosis.
Conclusions TSP-1/CD36 signaling could be a potential therapeutic target for AML.
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