| Objective: The matrix metalloproteinases (MMPs) including Mr 72,000 type IV collagenase (MMP-2, gelatinase A) and Mr 92,000 type IV collagenase (MMP-9, gelatinase B) play key roles in tissue remodeling and tumor invasion by digestion of extracellular matrix barriers and basement membranes. There were a series of pathological process in acute leukemia, such as the destruction of the marrow microenvironment, the releasing of immature blast cells from bone marrow to the peripheral blood. The abnormal expression of MMP-2/MMP-9 maybe cause extramedullary infiltrates or poor prognosis. The aim of the study was to investigate the gene and production of the two enzymes in AML patients, deduce the relationship between MMP-2/MMP-9 and the disease status of AML and if there were common pattern of MMP-2/MMP-9 secretion specific to a particular FAB subtype, extramedullary infiltrates, peripheral blood or bone marrow blast counts or to the prognosis. MMPs inhibitors maybe provide a unique method for treating acute myeloid leukemia, refractory to classical anti-cancer drugs, and may thus suppress recurrence.Methods: Reverse tanscription-polymerase chain reaction (RT-PCR) was applied to detect the gene expression of MMP-2 and MMP-9 in marrow mononuclear cells from healthy people and acute myeloid leukemia (AML) patients. Parts of samples were incubated for 24 hours and were detected the gene expression of MMP-2 and MMP-9. Zymography were applied to detect the MMP-2 and MMP-9 and their activity in the medium. The MMP-2 and MMP-9 expression in the leukemia cell lines HL-60 and K562 were also detected.Results: 1. The MMP-2 mRNA in 50 untreated AML samples was higher (the positive rate was 64%, the mean level of MMP-2/GAPDH was 0.508) than that of the control group ( the positive rates was 26.7% and the mean level was 0.122), the difference was significant, P<0.05; the MMP-9 mRNA had no significant difference (the positive rate was 44%, the mean level of MMP-9/GAPDH was 0.323) with that of the healthy control, P>0.05.2. The positive rate of the MMP-2 mRNA in 21 complete remission patients was 28.5% and the mean level was 0.183; that of the MMP-9 mRNA was 42.9% and the mean level was 0.333, there was no significant difference between the AML patients and the control group, P>0.05. 3. The MMP-2 mRNA in 15 patients in relapse was higher (the positive rate was 66.7% and the mean level was 0.643) than that of the control group, the difference wassignificant, P<0.05; but the MMP-9 mRNA had no significant difference (the positive rate was 46.7% and the mean level was 0.382) with that of the healthy control.4. The MMP-2/GAPDH and MMP-9/GAPDH in leukemia cell lines K562 were 1.124 and 1.007; and that in HL-60 were 0.826 and 0.609. 5. Zymographic analyses revealed the proMMP-2 and proMMP-9 presented in medium, the production of the enzymes paralleled with MMP-2 and MMP-9 mRNA.6. The MMP-2 and MMP-9 mRNA in 12 patients with extramedullary infiltrates were significant higher (the positive rate were 91.7% and 75%, the mean level were 0.941 and 0.931) than that of the patients without extramedullary infiltrates, P<0.05. 7. 11 of 42 (26.2%) MMP-2-positive cases appeared extramedullary infiltrates in 65 AML patients, the percentage was higher than that of MMP-2-negative patients (4.3%), the difference was significant, P<0.05. 9 of 29 (31%) MMP-9-positive cases appeared extramedullary infiltrates, the percentage was higher than that of MMP-9-negative patients (8.3%), the difference was significant, P<0.05. The enhanced expression of MMP-2 and MMP-9 in AML with extramedullary infiltrates show that they were essential to the invasion of leukemia cells. 8. 41 of 50 (82%) untreated AML patients were complete remission after chemotherapy. The MMP-2 mRNA inAML-CR group had no significant difference (the positive rate was 61%, the mean level was 0.483) with that of the AML-NR group, P>0.05. But MMP-9 mRNA in AML-CR group was significant lower (the positive rate was 34.1%, the mean level was 0.15...
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