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
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.
Penulis: I Dewa Gede Ugrasena,
Subijanto MS, Ketut Sudiana, Djajadiman Gatot
Kode Jurnal: jpbiologidd110049
