Polimorfisme Gen Timidilat Sintase-5UTR 3R/3R (TS-5’UTR 3R/3R) dan Metilentetrahidrofolat Reduktase C677T (MTHFR C677T) pada Anak dengan Leukemia Limfoblastik Akut yang Resisten dengan Metotreksat

Edit
Abstract: Childhood acute lymphoblastic leukemia (ALL) is the most common cancer in children. In Indonesia, it can now be cured in approximately 30–60% of patients. Drug resistance is the major cause of the treatment failure in childhood ALL. Despite the extensive studies, the mechanism of methotrexate (MTX) in the resistance of ALL is still not clear. The purpose of this study were to measure the invivo antileukemic effect of MTX and to identify the related responsible gene polymorphism of MTHFR C677T and TS 5-UTR 3R/3R in folate metabolism. This study prospectively evaluated the association of the MTHFR C677T and TS 5’-UTR 3R/3R gene polymorphisms by genotyping 155 pediatric ALL patients treated by the National 1994 ALL protocol and WK-ALL 2000 at Dr. Soetomo Hospital Surabaya. There was a significant correlation between MTHFR C677T and TS 5’-UTR 3R/3R gene polymorphism with MTX resistance. Children with MTHFR C677T polymorphism were 4 times more resistant than patients without MTHFR C677T polymorphism (p = 0.007). Patients with TS 5-UTR 3R/3R polymorphism were 6.4 times more resistant than patients without TS 5-UTR 3R/3R polymorphism (p = 0.001). Patients with a combination of 2 gene polymorphisms were 2.3 times more resistant to MTX than those with a single polymorphism. This study suggests that TS 5’-UTR 3R/3R is a dominant gene polymorphism related with MTX resistance in childhood ALL. The MTX resistance correlated with a combination of gene polymorphisms. In addition, there was no correlation between age, sex, and morphologic diagnosis with MTX resistance.
Keyword: polymorphism, , folate metabolism
Penulis: I Dewa Gede Ugrasena, Subijanto MS, Ketut Sudiana, Djajadiman Gatot
Kode Jurnal: jpbiologidd110049

Artikel Terkait :

Jp Biologi dd 2011