Marrow matrix metalloproteinases (MMPs) and tissue inhibitors of MMP in acute leukaemia: potential role of MMP-9 as a surrogate marker to monitor leukaemic status in patients with acute myelogenous leukaemia.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were demonstrated to have important implications in the progression and invasiveness of many malignant disorders. In contrast, the biological significance of these molecules in human leukaemias is not clear. We determined the levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in the bone marrow of 37 patients with acute myelogenous leukaemia (AML) and 18 patients with acute lymphoblastic leukaemia (ALL) before chemotherapy. Nineteen bone marrow donors served as normal controls. After chemotherapy, sequential measurements were done during the course in 19 AML patients. The levels of TIMP-1 and TIMP-2 were significantly higher and MMP-9 levels were significantly lower in the AML and ALL patients than in the normal controls. MMP-2 levels were higher in ALL, but not AML patients, compared with controls. Moreover, the levels of marrow MMP-2 and MMP-9 did not parallel the numbers of leukaemic blasts in the peripheral blood. MMP-9 levels were significantly lower in the AML patients who achieved a complete remission (CR) than in those who did not (8.71 +/- 8.15 ng/ml vs 26.13 +/- 27.75 ng/ml, P < 0.05). The AML patients with lower MMP-9 levels (< or = 4.4 ng/ml) tended to have longer survival time than those with higher levels (> 12 months vs 4 months, P = 0.12). In addition, MMP-9 levels in the AML patients at CR rose to the same range as the controls, but dropped again at relapse, demonstrating a close relationship of marrow MMP-9 with disease status of AML. Therefore, we conclude that the level of marrow MMP-9 may be a useful surrogate marker for monitoring disease status in AML and propose it as a potential prognostic factor.
Lin
Liang-In
LI
School of Medical Technology, College of Medicine, University Hospital, National Taiwan University, #7 Chung-Shan S. Road, Taipei, Taiwan.
Lin
Dong-Tsamn
DT
Chang
Chi-Jen
CJ
Lee
Cheng-Yeh
CY
Tang
Jih-Luh
JL
Tien
Hwei-Fang
HF
D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D001853:Bone Marrow / Q000737:chemistry*; D016022:Case-Control Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D011379:Prognosis; D012074:Remission Induction; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis*
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9