Importance of Altered Gene Expression of Metalloproteinases 2, 9, and 16 in Acute Myeloid Leukemia: Preliminary Study

Abstract

Acute myeloid leukemia is a group of hematological neoplasms characterized by a heterogeneous course and high mortality. The important factor in the neoplastic process is metalloproteinases, proteolytic enzymes capable of degrading various components of the extracellular matrix, which take an active part in modifying the functioning of the cell, including transformation to cancer cell. They interact with numerous signaling pathways responsible for the process of cell growth, proliferation, or apoptosis. In the present study, changes in the expression of MMP2, MMP9, and MMP16 genes between patients with AML and people without cancer were examined. The impact of cytogenetic changes in neoplastic cells on the expression level of MMP2, MMP9, and MMP16 was also assessed, as well as the impact of the altered expression on the effectiveness of the first cycle of remission-inducing therapy. To evaluate the expression of all studied genes MMP2, MMP9, and MMP16, SYBR Green-based real-time PCR method was used; the reference gene was GAPDH. For two investigated genes MMP2 and MMP16, the lower expression level was observed in patients with AML when compared to healthy people. The MMP9 gene expression level did not differ between patients with AML and healthy individuals which may indicate a different regulation of gene expression in acute myeloid leukemia. However, no correlation was observed between the genes' expression of all tested metalloproteinases and the result of cytoreductive treatment or the presence of cytogenetic changes. The obtained results show that the expression of MMP2 and MMP16 genes is reduced while the expression of MMP9 is unchanged in patients with acute myeloid leukemia. This may indicate a different regulation of the expression of these genes, and possible disruptions in gene transcription or posttranscriptional mechanisms in the MMP2 and MMP16 genes, however, do not affect the level of MMP9 expression. Obtained results in AML patients are in contrary to various types of solid tumors where increased expression is usually observed.