Plasma Gelatinolytic Activity in Leukemias.

Gelatinase A (Matrix Metalloproteinase 2, MMP-2) and B (Matrix Metalloproteinase 9, MMP-9) are secreted by connective tissue, endothelial, epithelial and hematopoietic cells. Elastase and gelatinases produced by granulocytes are released in whole blood in response to varied stimuli. They induce breakdown of connective tissue and play an important role in processes of cell transmigration and tissue remodeling. The aims of this study were to determine and compare the plasma concentration of PMN elastase and the gelatinase activity in patients with chronic myelogenous leukemia (CML, n=16), acute myeloblastic leukemia, AML, n=53 and acute lymphoblastic leukemia, ALL, n=18) and in healthy persons (n=22). We measured activity of MMP-2 and MMP-9 using gelatine zymography and concentration of elastase from polymorphonuclear leukocytes (PMN) in complex with alpha1-proteinase inhibitor using ELISA. The MMP-9 activity in plasma from patients with CML was higher than that from AML, ALL and reference groups. The MMP-9 activity in AML and ALL group was lower than in healthy persons. There was no significant difference in the MMP-2 levels between the plasma samples from patients with CML or ALL and those from healthy subjects, but MMP-2 activity was lower in the reference group than in AML. PMN elastase concentration in plasma from the healthy reference group was lower than that from CML and AML patients. Furthermore, PMN elastase concentration in plasma from CML patients was higher than that from AML and ALL. We found significant correlation between MMP-9 activity and white blood cells count in the reference group (r=0,56), CML group (r=0,70) and AML group (r=0,44). The PMN elastase concentration increased proportionally to the white blood-cell count (r=0,51) in plasma from patients with CML only. There was significant relationship between the count of granulocytes in different stages of maturation with PMN elastase and MMP-9 activity: promyelocytes (r=0,73 for elastase and r=0,75 for MMP-9), myelocytes (r=0,63 and r=0,79), metamyelocytes (r=0,56 and r=0,83), band neutrophils (r=0,64 and r=0,74), segmented neutrophils (r=0,73 for MMP-9) and eosinophils (r=0,64 for MMP-9) in blood from CML patients. Increased MMP-9 activity was correlated with increased MMP-2 activity in the reference group (r=0,58) and AML group (r=0,50), however it was correlated with decreased MMP-2 activity in the CML group (r=−0,59). In the CML group it was observed that decreased MMP-2 activity correlated with an increased count of: blasts (r=−0,64), promyelocytes (r=−0,77), myelocytes (r=−0,63), metamyelocytes (r=−0,64) and band neutrophils (r=−0,60). Gelatin zymography can be employed to display differences of plasma MMP-2 and MMP-9 activity between patients with chronic myelogenous leukemia, acute leukemia and healthy persons.