Nihal İNANDIKLIOGLU, Osman DEMİRHAN, İbrahim BAYRAM, Atila TANYEL, İ

Akut lenfoblastik lösemili çocuklarda MMP-2, MMP-9, TIMP-1, TIMP-2 ve VEGF-A genlerinin ekspresyon ve metilasyon seviyelerindeki değişiklikler

Amaç: Bu makalenin amacı, çocukluk çağı akut lenfoblastik lösemi (ALL) tanısı almış hastalarda matriks metaloproteinazlar (MMP'ler), doku inhibitörleri metaloproteinazlar (TIMP'ler) ve vasküler endotelyal büyüme faktörünün (VEGF) genlerinin ekspresyon ve metilasyon düzeylerini ve bunların klinik bulgularla ilişkisini göstermektir. Gereç ve Yöntem: Bu çalışmada, çocukluk çağı ALL hastaları ile sağlıklı çocuklar arasında MMP2, MMP9, TIMP1, TIMP2 ve VEGF-A genlerinin ekspresyon düzeyini ve metilasyon yüzdesini belirledik. Ekspresyon ve metilasyon analizleri RT-PCR ile yapıldı. MMP2, MMP9, TIMP1, TIMP2, VEGF-A ve diğer klinik parametrelerin sonuçları iki grup arasında karşılaştırıldı. Bulgular: Hastalarda MMP2 (2.55-kat), MMP9 (5.06-kat), TIMP1 (2.91-kat) ve VEGF-A (4.76-kat) ekspresyon seviyeleri anlamlı olarak yüksekti, ancak aynı sonuçlar TIMP-2 için geçerli değildi. Hastalarda MMP2 (% 29.74), MMP9 (% 30.98), TIMP2 (% 11.91) ve VEGF-A (% 6.55) metilasyon düzeyleri kontrollere göre anlamlı derecede yüksekti. Sonuç: Verilerimiz MMP2, MMP9 ve VEGF-A genlerinin yüksek ekspresyon ve metilasyon seviyelerine sahip olduğunu gösterdi. Bu sonuçlar, çocukluk çağı ALL’de bu karmaşık yapıyı daha ileri çalışmalar için ilgi çekici hale getirmekte ve araştırılması gerektiği vurgusunu pekiştirmektedir.

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

Purpose: The aim of this article is to show the expression and methylation levels of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and vascular endothelial growth factor (VEGF)genes in patients diagnosed with childhood acute lymphoblastic leukemia (ALL) and their relationship with clinical findings. Materials and Methods: In this study, we determined the expression level and methylation percentage of MMP2, MMP9, TIMP1, TIMP2 and VEGF-A genes between patients with childhood ALL and healthy children. Expression and methylation analyzes were performed by RT-PCR. The results of MMP2, MMP9, TIMP1, TIMP2, VEGF-A and other clinical parameters were compared between the two groups. Results: The expression levels of MMP2 (2.55-fold), MMP9 (5.06-fold), TIMP1 (2.91-fold) and VEGF-A (4.76-fold) was significantly higher in the patients, but the same results were not found for TIMP-2. The methylation levels of MMP2 (29.74%), MMP9 (30.98%), TIMP2 (11.91%) and VEGF-A (6.55%) were significantly higher in the patients than in the controls. Conclusion: MMP2, MMP9 and VEGF-A genes have high expression and methylation levels. These results make this complex structure intriguing in childhood ALL for further studies and reinforce the emphasis that it should be investigated.

Keywords:

Acute lymphoblastic leukemia, MMP, TIMP, VEGF-A,

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