Expression of matrix metalloproteinase-9 and tissue inhibitor metalloproteinase-1 in childhood acute lymphoblastic leukemia

Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate the turnover of the extracellular matrix and may modulate the biology of hematopoietic cells. They are key players in many physiological and pathological processes such as development, angiogenesis, connective tissue remodeling, as well as tumor invasion and metastasis.Objectives: Estimate marrow MMP-9 expression and detect the levels of TIMP-1 in patients with acute lymphoblastic leukemia (ALL) and correlate these results to the clinical characteristics and survival studies of the patients.Materials and methods: Thirty newly diagnosed patients with childhood ALL and 10 healthy control children were studied using real-time PCR for the measurement of mRNA expression of the MMP-9 gene and using the flow cytometric technique for the detection of intracytoplasmic protein levels of TIMP-1.ResultsMMP-9 expression was significantly lower in patients compared with the control group, whereas TIMP-1 expression showed no significant difference between both the groups. No significant difference was observed between patients with a high MMP-9 expression and low MMP-9 expression in terms of clinical and laboratory data, except for the platelet count, which was higher in patients with a high MMP-9 expression. Besides CD34 expression, TIMP-1 expression was not significantly related to clinical and laboratory data of the patients studied. The median TIMP-1 expression, but not MMP-9, was significantly associated with the initial response to therapy. However, neither MMP-9 nor TIMP-1 expression was significantly associated with the relapse rate, overall survival, or event-free survival.Conclusion: The clinical importance of MMP-9 and TIMP-1 expression in childhood ALL is still unclear. Further larger studies with a longer follow-up period are recommended to confirm the prognostic value of MMP-9 and TIMP-1 expression in pediatric ALL patients.