Importance of plasma matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinase (TIMP) in development of fibrosis in agnogenic myeloid metaplasia

Tissue inhibitors of metalloproteinase (TIMP) and matrix metalloproteinases (MMP) are key elements in the formation, remodeling and degradation of matrix protein. Bone marrow fibrosis in AMM, with deposition, not only of interstitial and basement membrane collagen but also of fibronectin, vitronectin, laminin and proteoglycans, results from a disturbed balance between synthesis and proteolytic degradation of matrix protein. Although TIMP and MMP play important roles in the development of fibrosing diseases of skin, liver and lung, only a few studies of TIMP and MMP in the formation of bone marrow fibrosis in AMM have been published. The literature shows that TIMP-1 (both the total, complex and the free form) is significantly increased in AMM and other myeloproliferative syndromes (including polycythemia vera (PV) and essential thrombocytosis (ET)), while MMP-3 is significantly decreased, and levels of MMP-2 and MMP-9 are not different from control values. Variance from control values for both TIMP-1 and MMP-3 is more evident in AMM than in PV and ET, thus further suggesting bone marrow fibrosis in AMM results from enhanced TIMP and decreased MMP activities.