Expression Of MMP-2 And -9 In Acute Leukemia And A Possible Link In Leukemic Cell Invasion

Objective: Matrix metalloproteinases (MMPs) are a group of structurally homologous and functionally related Zn2+ or Ca2+ dependent endopeptidases. Many factors operate to control the expression and activity of individual MMPs. The tissue inhibitors of metalloproteinases (TIMPs) are correspondingly widespread in tissue distribution and function as highly effective MMPs inhibitors. The balance between MMPs and TIMPs is critical for the control of proteolysis. All these regulation are very important in physiological processes like wound healing and tissue morphogenesis. Once the balance was broken, MMPs could destroy local tissue architecture to allow tumor growth and break down basement membrane (BM) in facilitating metastasis. Many studies show that MMPs can induce neoangiogenesis and metastasis. There have been abundant researches to support the matrix-degrading function of MMPs in tumor invasion. But seldom reports documented the relationship between the MMPs and leukemia. In order to investigate the mechanism of leukemic cells malignant transformation and infiltration, and thus provide therapy basis for preventing and treating acute leukemia(AL), our study examined the expression of MMP-2 and MMP-9 in bone marrow cells of untreated acute leukemia, relapse stageof acute leukemia, complete remission (CR) stage of acute leukemia and normal control by in situ hybridization.Materials and method: (1) Subjects were divided into four groups: (D The untreated AL group (n=32, Male 16 , Female 16, Mean age 37.3Y) including acute lymphoblastic leukemia(ALL) 12 cases and acute nonlymphoblastic leukemia (ANLL) 20 cases. According to the diagnostic standard worked out by FAB in 1985, ANLL were further subdivided into M₂ 8 cases, M₃ 2 cases, M4 6 cases, M5 4 cases. (2) The relapse stage of AL group (n=ll, Male 6, Female 5, Mean age 27.6Y) including ALL 5 cases, ANLL 6 cases. According to the diagnostic standard worked out by Suzhou meeting in 1987, ANLL were further subdivided into Ma 3 cases, M4 2 cases, M₅ 1 case. (3) The CR stage of AL group (n=20, Male 10 , Female 10, Mean age 27.6Y) including ALL 7 cases and ANLL 13 cases. According to the diagnostic standard worked out by Suzhou meeting in 1987, ANLL were further subdivided into Ma 7 cases, M₃ 3 cases, M₄ 3 cases. (D The normal control group (n=32, Male 16 , Female 16, Mean age 37.3 Y). (2) Collecting the mononuclear cells of bone marrow of all subjects, test the positive rate of MMP-2 and MMP-9 by in situ hybridization. (3) The results were analyzed with chi-square test by SPSS 10.0, and we established the standard of statistic significance as a=0.05.Results: (1) The positive rate of MMP-2 in these four groups decreased gradually. They are (69.22?15.97) %, 206.03?1.82; (50.36+9.52) %, 138.09+21.22; (25.95+20.04) %, 74.90?3.52 and (15.05 + 5.04) %, 39.00?3.10. There are significant differences among these four groups(p<0.05). (2) The positive rate of MMP-9 in these four groups also decreased gradually. They are (70.03?3.55) % 204.72 + 38.90; (51.36 + 8.25) %, 145.18+26.17; (24.55 + 19.19) %, 69.40 + 60.21 and (18.50 + 6.44) %, 48.90 +17.31. There are significant differences among every two groups(/?<0.05), except the CR group and normal control group(p>0.05). (3) The positive rate of MMP-2 in untreated ALL group and untreated ANLL (M4+Ms)group are significant higher than that in untreated ANLL (non M4+Ms) group(p<0.05), and there is no significant difference between the former twogroups(P>0.05). The numbers are(76.92+13.55) %, 230.42 + 58.29; (76.40+9.74) %, 214.60+ 30.37 and (52.80+13.73) % 168.20+41.36. (4) The positive rate of MMP-9 in untreated ALL group and untreated ANLL (M4+M₅)group are significant higher than that in untreated ANLL (non M₄+Ms) group(P<0.05), and there is no significant difference between the former two groups(p>0.05). The numbers are (76.25 + 7.15) % 217.42+32.92; (78.50+6.90) %. 217.80?9.81 and (54.20+10.69) %, 176.40 ?1.72.Conclusion: (1) MMP-2 and MMP-9 overexpress in untreated acute l...