Urokinase Plasminogen Activator Receptor and Soluble Matrix Metalloproteinase-9 in Acute Myeloid Leukemia Patients: A Possible Relation to Disease Invasion

Abstract

Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) and metalloproteinase (MMP) family play a crucial role in the matrix degradation and tissue remodeling process characteristic of malignant disorders. The receptor for urokinase plasminogen activator (uPAR) serves to localize and intensify the action of UPA and is expressed on the surface of malignant cells. Although the biological significance of MMP-9 and soluble urokinase receptor in growth and progression of lymphoid neoplasm is understood, its clinical significance in acute myeloid leukemia (AML) has not been fully elucidated. In this study, we determined the levels of soluble urokinase-type plasminogen activator receptor (suPAR), cellular uPAR and sMMP-9 in 43 newly diagnosed AML patients at diagnosis, before chemotherapy, and also studied 10 normal subjects served as a control group. After chemotherapy suPAR and MMP-9 were determined at remission and relapse. The levels of suPAR, cellular PAR were significantly higher (P=0.001, 0.001) and MMP-9 was significantly lower (P=0.001) in AML patients at diagnosis as compared to controls. suPAR and MMP-9 levels were significantly lower in AML patients who achieved complete remission (CR) as compared to those who did not (P=0.001 for both). Levels of suPAR and MMP-9 were significantly correlated to peripheral blood blast cells (r=0.88, P=0.001; r=0.65, P=0.001, respectively) and blast cell distribution ratio (BCDR, r=0.84, P=0.001; r=65, P=0.001, respectively). suPAR, cellular PAR and MMP-9 were significantly higher in patients with extramedullary infiltration as compared with those without (P=0.001, 0.001, <0.05). The suPAR, cellular uPAR, and MMP-9 levels were uneven in AML FAB subtypes being highest in M5(P<0.05 for all). MMP-9 and suPAR levels were correlated with the disease status. In AML survivors, MMP-9, cellular uPAR and suPAR were significantly lower as compared to non-survivors (P=0.001 for all).In conclusion, MMP-9 and suPAR levels might be used as a marker for disease activity and may contribute to blast cell dissemination. MMP-9 and suPAR may be target molecules in the strategy of treatment of AML.