The Roles Of MMP-2, TIMP-2 And MMP-9 In Acute Leukemia

Objective:To investigate the expression of matrix metalloproteinase-2 (MMP-2),matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in acute leukemia (AL) and normal control.Methods:Supernatant of bone marrow were harvested from leukemia patients and the normal control. The concentration of MMP-2,MMP-9 and TIMP-2 in bone marrow supernatant were measured in 26 patients with new diagnosed ANLL (Acute non-lymphocyte Leukemia, ANLL),9 patients with new diagnosed ALL (Acute Lymphocyte Leukemia, ALL),12 patients with relapsed leukemia,27 patients gained complete ression and 8 normal control.The MMP-2 and TIMP-2 gene expression were determined in 35 newly diagnosed acute leukemia patients and 12 relapsed acute leukemia patients.Results:The levels of MMP-2 were significantly higher and MMP-9 levels were significantly lower in the newly diagnosed, relapsed and complete remission leukemia patient than in the normal controls. The levels of TIMP-2 were no difference in four groups.In the patients newly diagnosed with acute leukemia (Acute leukemia, AL), the levels of MMP-2 and TIMP-2 were higher in ALL patients than in ANLL and normal controls. The levels of MMP-9 in ALL and ANLL were no difference and both were lower than normal controls.In the newly diagnosed and relapsed leukemia patients, the levels of MMP-2 and TIMP-2 in ALL with extramedullary infiltration were significantly higher than in patients of ALL without extramedullary infiltration and ANLL with or without extramedullary infiltration. In addition, the ratio of MMP-2/TIMP-2 didn't have difference in ALL and ANLL patients with or without extramedullary infiltration, and all were significant higher than normal controls.Moreover, the concentration levels of MMP-2,MMP-9 and TIMP-2 of marrow did not correlated with the age, sex, the rate of blasts cells in bone marrow, white blood cells and the numbers of leukemic blasts in the peripheral blood.For the newly diagnosed acute leukemia, the levels of MMP-2,MMP-9 and TIMP-2 in the patients who gain complete remission(CR) were no difference than patients without complete remission after chemotherapy. In addition,7 patients who gained CR after chemotherapy, the MMP-2 and TIMP-2 levels didn't had difference before and after chemotherapy, the levels of MMP-9 was elevated to the same range as the controls after chemotherapy.The MMP-2 and TIMP-2 mRNA expression in newly diagnosed and relapsed leukemia ALL patients with extramedullary infiltration were higher than in patients of ALL without extramedullary infiltration and ANLL with or without extramedullary infiltration.Conclusion:The MMP-2, MMP-9 and TIMP-2 play important roles in the progression and extramedullary infiltration of AL.