In vitro secretion of matrix metalloprotease 9 is a prognostic marker in childhood acute lymphoblastic leukemia

Matrix metalloproteases (MMPs) are endopeptidases involved in tumor cell invasion. Childhood acute lymphoblastic leukemia (ALL) is characterized by its capacity to infiltrate different organs. We analyzed the expression of MMP-2, -9, -14 and TIMP-1 and -2 in a prospective study on 86 children with newly diagnosed ALL (73 B- and 13 T-lineage) and 9 children at relapse with B-ALL. Membrane-bound and intracytoplasmic MMPs and TIMPs were analyzed by flow cytometry, and secreted MMPs were quantified by ELISA. In patients at relapse, MMP-14 was present in a greater proportion of the B-ALL cell population than at diagnosis. In patients with peripheral infiltration, intracytoplasmic MMP-9 was significantly higher than in patients without infiltration. ROC curve and Kaplan–Meier curve analysis showed that a high secretion of MMP-9 (>2450 pg/ml/106 cells) was associated with a lower overall survival rate, suggesting that the secretion of MMP-9 is an independent prognostic factor in childhood B-ALL.