UNIVERSITAS AIRLANGGA



Detail Article

BIOSAINS

ISSN 1412-1433

Vol. 13 / No. 2 / Published : 2011-05

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Original Article :

Gene polymorphism of mthfr c677t and ts 5’-utr 3r/3r, on childhood acute lymphoblastic leukemia resistance to methotrexate

Author :

  1. I Dewa Gede Ugrasena*1
  2. Subijanto MS*2
  3. Ketut Sudiana*3
  4. Djajadiman Gatot*4
  1. Departemen Ilmu Kesehatan Anak RSUD Dr. Soetomo, Fakultas Kedokteran Universitas Airlangga
  2. Departemen Ilmu Kesehatan Anak RSUD Dr. Soetomo, Fakultas Kedokteran Universitas Airlangga
  3. Departemen Patologi Anatomi Fakultas Kedokteran Universitas Airlangga
  4. Fakultas Kedokteran Universitas Indonesia

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, , acute lymphoblastic,


References :

Chiusolo P, Reddiconto G, Cimino G, et al. ,(2004) Methylenetetrahydrofolate reductase genotypes do not play a role I acute lymphoblastic leukemia pathogenesis in Italian population. - : Haematologica

Gatot D,(1991) Nature of Leukemia. Jakarta : PTB IKA FKUI

Giaccone G, Pinedo HM,,(2008) Drug Resistance. Free University Hospital Netherlands : Departement of Oncology, the Netherlands

Giaccone G, Pinedo HM,,(2008) Drug Resistance Netherlands : Departement of Oncology, the Netherlands

Kanerva Jukka,(2001) Prognostic factors in childhood acute lymphoblastic leukemia (ALL) Helsinki : Hospital for Children and Adolescents University of Helsinki Finland.





Archive Article

Cover Media Content

Volume : 13 / No. : 2 / Pub. : 2011-05
  1. Antimalarial Activity And Mechanism Of Action Of Flavonoid Compounds Isolated From Artocarpus Champeden Spreng Stembark
  2. Studi On The Espression Of Tgf-b1 Mmp-9, Collagen Type-i, Collagen Tipe-iv, Glomerulosclerosis, Interstisial Fibrosis, And Albuminuria In Hephrotoxic Docorubin And Nephroprotective Pentoxifyllin Events On Male Swiss-strain Mice
  3. Characterization Of Physical Properties From Human Enamel Induced By Nd:yag Pulsed Laser Based On Laser Speckle Imaging System
  4. Protein Expression Of Cox-2 In High And Low Response In Nasopharynx Carcinoma After Radiotherapy
  5. Gene Polymorphism Of Mthfr C677t And Ts 5’-utr 3r/3r, On Childhood Acute Lymphoblastic Leukemia Resistance To Methotrexate
  6. Effective Growth Medium, Light Intensity And Length Of Radiation For Culturing Isolated Microcystis From Sutami Reservoir In Laboratory
  7. Nutrition And Iron Status In Children With Tb Parents, Their Role On Infection And Disease

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