Prognostic relevance of circulating matrix metalloproteinase‐2 in acute myeloid leukaemia patients

Abstract

Matrix metalloproteinases (MMPs) were postulated to have important implication in progression and invasiveness of many malignant disorders. On the other hand the biological role of MMP-2 in acute myeloid leukaemia (AML) is not fully clear. Serum samples from 37 adult patients with AML had been taken before chemotherapy was administered. In addition 20 out of the 37 patients were analysed again after achieving complete remission (CR). Ten samples from healthy volunteers were evaluated as the control. Total MMP-2 levels were measured using ELISA Kit obtained from R&D system. MMP-2 serum levels were significantly lower in pretreatment AML patients than that in the normal controls (p = 0.000) and in CR (p = 0.007). No significant correlations were detected between pretreatment sMMP-2 levels and FAB subtypes, peripheral blood blast cell counts, peripheral blood WBCs, bone marrow blast cell counts or blast cell distribution ratio. The prognostic value of MMP-2 was evaluated by dividing AML patients into high and low MMP-2 groups using the pretreatment median MMP-2 level of the AML group as the cut-off. The authors found that patients in the high group survived for a significantly shorter time than those patients in the lower MMP-2 group. High pretreatment levels of sMMP-2 among AML patients were associated with poor survival. Prospective studies are recommended to establish the clinical value of longitudinal sMMP-2 measurement.

Enhanced invasiveness of drug‐resistant acute myeloid leukemia cells through increased expression of matrix metalloproteinase‐2

“…Importantly, we found that along with the acquisition of drug resistance, there was a marked increase in the expression and activity of MMP-2, which has been known as a marker and key factor in aggressive malignant tumor cells. 7,8,34 In addition to the results from in vitro drug-resistant AML models, invasion assay using primary BM cells supports the suggestion that the elevated level of MMP-2 activity may directly regulate the invasiveness of drug-resistant BM cells. Recently, combined therapy of synthetic MMP inhibitors and anticancer agents has been evaluated to decrease metastasis and improve therapeutic effect in broad range of tumors.…”

Targeting CD13 (aminopeptidase-N) in turn downregulates ADAM17 by internalization in acute myeloid leukaemia cells

“…In contrast, proMMP-2/-9 patterns were not subtype-restricted. Our data agree with studies in which proMMP-2/-9 levels and FAB subtypes were not correlated [20, 35]. It remains to be seen whether ADAM17 levels are predictive of chemoresistance or responsiveness to treatment in AML.…”

Aberrant Proliferative and Apoptotic Pathways in Acute Lymphoblastic Leukemia (ALL): Molecular Therapies to Overcome Chemo-Resistance

“…Several studies have demonstrated the existence of a crosstalk between the endothelium and leukemic cells, in which leukemia cells stimulate BM endothelium and promote de novo angiogenesis and neovascularisation, while BM endothelium promoted leukemia cell survival through modulation of antiapoptotic bcl-2 family members (Veiga et al, 2006). Another study by Aref et al (2007) described in B-ALL an abnormal expression of matrix metalloproteinases (MMP), which is a further class of angiogenesis and tumor progression regulators produced by both stromal and leukemic cells (Aref et al, 2007) A further interesting aspect related to BM microenvironment and leukemia cells interactions regards the role of BM microenvironment on lineage commitment and differentiation. Several studies have indeed demonstrated that BM microenvironment can drive lineagespecific differentiation in leukemia by modulating different cytokines and other soluble components (Kankuri et al, 2008;Wei et al, 2008).…”