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The core of the tumor microenvironment in the hematological system is formed by bone marrow stromal cells (BMSCs). In the present study, we explored the interaction between the urokinase plasminogen activator (uPA) system and the leukemia bone marrow microenvironment (BMM). We established BMSCs-HL60 and HS-5-K562 co-culture models in direct contact mode to simulate the BMM in leukemia. In BMSCs-HL60 co-culture model, the expression levels of uPA, uPA receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1) and vascular endothelial grow