The investigation of VEGF-A, MMP-2, MMP-9, TIMP-1 and TIMP-2 genes expression alterations and methylation levels in children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia is a malignant disease of lymphocytic progenitors and originates from single B or T cell clone. The accumulation and proliferation of the blast cells in bone marrow leads to bone marrow supression. VEGF-A, TIMP-1, TIMP-2, MMP-2 and MMP-9 genes have been associated with invasion and metastasis of solid tumors but the effects of these genes for the etiology of hematologic cancers are not known completely. In our study, 26 patients diagnosed with a acute lymphoblastic leukemia were included in Cukurova University Faculty of Medicine, Pediatric Oncology Unit. The control group consisting of 26 healthy children with the same age and gender and have no family history for cancer was recorded. The expression and methylation levels of vascular endothelial growth factor-A (VEGF-A), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) genes were detected by RT-PCR method in children with ALL. There were significant differences in expression of VEGF-A (p<0,05), TIMP-1 (p<0,05), MMP-2 (p<0,05) and MMP-9 (p<0,05) of ALL patients compared to the control group, whereas any significant difference was not found in TIMP-2 (p>0,05) level statistically. Percentage of methylation of VEGF-A, TIMP-2, MMP-2 and MMP-9 genes were significantly higher in ALL patients than that of control group (p<0,05). In our study, age, leukocyte and platelet count, hemoglobin level, CD surface antigens, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and the classification criteria of ALL were evaluated statistically in all patients. In conclusion, VEGF-A, TIMP-1, TIMP-2, MMP-2 and MMP-9 expression and methylation levels could play an important role in the pathogenesis of ALL and help provide new insights into the investigation of target genes for the following up clinically in children diagnosed with ALL. Key Words: Acute lymphoblastic leukemia, VEGF-A, MMP-2, MMP-9, TIMP-1, TIMP-2