, vol. 26, issue 1, pp. 758-768, 2021.
BACKGROUND: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed.
METHODS: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- cancer stem cells (CSCs) were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis.
RESULTS: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, ], and CSCs CD34CD38 [1 (0.03-18.6) versus 0.3 (0.01-1.1), expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, area under curve (AUC) of MMP-2 were (80.3%, 53.3% and 0.568, = 0.404), and of MMP-9 were (53.9%, 40% and 0.660, = 0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, , and that of CD34CD38 CSCs were (78.9%, 73.3% and 0.855, . Increased TIMP-1 expression associated with the high-risk disease ). CD34CD38 CSCs and MMP-2 overexpression associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 ( ). TIMP-1 overexpression is associated with shorter DFS and OS rates ( and ). Multivariate logistic regression analysis showed that both TIMP-1 [ ], and CD34CD38 CSCs [ ] could be potential independent diagnostic factors for pediatric ALL.
CONCLUSION: TIMP-1 and CD34CD38 CSCs could be possible useful diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.