Abstract
Amaç: Folat ilişkili genlerin, polimorfizminin akut lenfoblastik lösemiye (ALL) yatkınlığı etkilediği bildirilmiştir. MTHFR geninde tanımlanmış tek nükleotid polimorfizmlerinden (TNP) T677T veya C1298C allelleri vahşi tip allelere göre (C677C ve A1298A) enzim aktivitesinde azalmaya yol açar. MTHFR gen polimorfizmlerinin ayrıca ALL tedavisinde sıklıkla kullanılan antifolat etkili ilaçların metabolizmasını etkileyerek toksisiteyi artırdığı ve böylece sağkalımı etkilediği bildirilmiştir. Çalışmada kliniğimizde izlediğimiz ALL tanılı hastalarımızda MTHFR’nin her iki polimorfizmlerinin sağkalım üzerinde etkisini inceledik.Gereç ve Yöntemler: B hücreli ALL tanısıyla BFM TRALL 2000 protokolü alan hastaları geriye dönük olarak incelendi. Sekizinci gün mutlak blast sayısı, 15 ve 33. gün kemik iliği verileri yanı sıra MTHFR polimorfizmleri kaydedildi.Bulgular: Çalışmaya 33 erkek, 23 kız, tanı yaşı ortalama 4.73 yıl olan (en küçük-en büyük 1.3-16.75 yıl) toplam 56 hasta alındı. Bu hastaların prognozu incelendiğinde 5 hastanın relaps olduğunu gördük. Çalışmamızda C677T veya A1298C allelinin farklı kombinasyonlarını taşıyan bireylerin sağkalım ve olaysız sağkalımları arasında ilişki bulunamadı.Sonuç: Çalışmamızda MTHFR polimorfizmlerinin ALL’li çocuklarda sağkalım üzerine etkisi gösterilememiştir. Daha çok olguyla yapılacak bir çalışmanın daha kesin sonuçlara varmamızı sağlayacağına inanıyoruz.
References
- Pui CH, Mullighan CG, Evans WE, Relling MV. Pediatric acute lymphoblastic leukemia: Where are we going and how do we get there? Blood 2012;120:1165-74.
- Mackall CL. In search of targeted therapies for childhood cancer. Front Oncol 2011;1:18.
- Aplenc R, Lange B. Pharmacogenetic determinants of outcome in acute lymphoblastic leukaemia. Br J Haematol 2004;125:421-34.
- Barbosa CG, Souza CL, Neto JPM, Arruda MGB, Barreto JH, Reis MG, et al. Methylenetetrahydrofolate reductase polymorphisms in myeloid leukemia patients from Northeastern Brazil. Genet Mol Biol 2008;31:29-32.
- de Jonge R, Tissing WJ, Hooijberg JH, Jansen G, Kaspers GJ, Lindemans J, et al. Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood 2009;113:2284- 9.
- Hider SL, Bruce IN, Thomson W. The pharmacogenetics of methotrexate. Rheumatology (Oxford) 2007;46:1520-4.
- Yang L, Hu X, Xu L. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: A meta-analysis. Tumour Biol 2012;33:1445-54.
Abstract
Objective: Folic acid-related genes’ polymorphisms have been related with a predisposition to acute lymphoblastic leukemia (ALL). Two common polymorphic sites on MTHFR gene; T677T and C1298C may decrease the activity of this enzyme compared to the wild type alleles (C677C and A1298A). The polymorphism may affect the metabolism of antifolate drugs and cause increased drug toxicity and decreased survival. In this study, we evaluated the effect of two frequent polymorphisms on survival of children with ALL.Material and Methods: We retrospectively evaluated patients who had been diagnosed with B cell ALL and then treated with the BFM TRALL 2000 treatment protocol. We recorded their absolute blast counts at day 8, and bone marrow evaluation at days 15 and 33 as well as MTHFR polymorphisms. results: Fifty-six patients [male/female: 33/23, mean age at diagnosis 4.73 years range 1.3-16.75 years)] were included in the study. Out of the 56 patients, 5 developed relapse. There was no relationship between different polymorphic alleles of the MTHFR gene with survival and event-free survival. conclusion: We did not observe any effect of MTHFR polymorphisms on survival of children with ALL. We believe further studies with a larger group of patients are necessary to draw a firm conclusion
References
- Pui CH, Mullighan CG, Evans WE, Relling MV. Pediatric acute lymphoblastic leukemia: Where are we going and how do we get there? Blood 2012;120:1165-74.
- Mackall CL. In search of targeted therapies for childhood cancer. Front Oncol 2011;1:18.
- Aplenc R, Lange B. Pharmacogenetic determinants of outcome in acute lymphoblastic leukaemia. Br J Haematol 2004;125:421-34.
- Barbosa CG, Souza CL, Neto JPM, Arruda MGB, Barreto JH, Reis MG, et al. Methylenetetrahydrofolate reductase polymorphisms in myeloid leukemia patients from Northeastern Brazil. Genet Mol Biol 2008;31:29-32.
- de Jonge R, Tissing WJ, Hooijberg JH, Jansen G, Kaspers GJ, Lindemans J, et al. Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood 2009;113:2284- 9.
- Hider SL, Bruce IN, Thomson W. The pharmacogenetics of methotrexate. Rheumatology (Oxford) 2007;46:1520-4.
- Yang L, Hu X, Xu L. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: A meta-analysis. Tumour Biol 2012;33:1445-54.
Details
| Other ID | JA39PE79TN |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | August 1, 2017 |
| Submission Date | August 1, 2017 |
| Published in Issue | Year 2017 Volume: 11 Issue: 3 |
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