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High frequency of the 3R/3R polymorphism in the thymidylate synthase enhancer region in Indonesian childhood acute lymphoblastic leukemia IDG Ugrasena; Sutaryo Sutaryo; Edy Supriadi; Laura Vroling; Jacqueline Cloos; Jan Hendrik Hooijberg; AJP Veerman
Paediatrica Indonesiana Vol 46 No 3 (2006): May 2006
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14238/pi46.3.2006.103-12

Abstract

Background Deoxyuridylate monophosphate (dTMP) is neces-sary for DNA synthesis and thymidylate synthase (TS) is an im-portant target of cancer chemotherapy. Ethnic variations of thepolymorphic tandem repeat sequence in the enhancer region ofthe TS promoter has previously been described to influence theoutcome of acute lymphoblastic leukemia (ALL). A triple repeat isassociated with a higher TS gene expression than a double re-peat, resulting in poorer outcome of ALL patients treated with anti-folate methotrexate (MTX).Objective In this study, we determined the incidences of TS andmethylenetetrahydrofolate reductase (MTHFR) polymorphism andethnic variations between Indonesian and Caucasian ALL cellsamples obtained at diagnosis. Furthermore, we determined theinvolvement of TS polymorphisms in MTX sensitivity using athymidilate synthase inhibition assay (TSIA).Methods ALL cell samples were obtained at diagnosis from 101Indonesian and 157 Caucasian children treated with MTX prospec-tively. Genotyping for TS and MTHFR was analyzed by Genescanand Lightcycler. TS polymorphism was determined by PCR assayand MTHFR polymorphism and was analyzed by melting curveanalyses on lightcycler.Results Homozygous TS triple repeats were more than twice ascommon in Indonesian samples (76.3%) than in Caucasian samples(33.1%). Heterozygotes of the MTHFR mutations were seen in 15%of the screened Indonesian samples.Conclusion There are significant ethnic variations in TS generegulatory elements of leukemic cells. A difference was found be-tween the MTX sensitivity and a double or triple repeat in the Cau-casian ALL group. The samples with a triple repeat show a shift intheir distribution towards hypersensitivity to MTX. Further investi-gation on Indonesian samples may give insight in the role of poly-morphisms in MTX sensitivity
Hyperglycemia in Childhood Acute Lymphoblastic Leukemia during Induction Chemotherapy Nengcy Erlina Tasik Rerung; Cahyadi, Andi; Nur Rochmah; Maria Christina Shanty Larasati; Andarsini, Mia Ratwita; Muhammad Faizi; IDG Ugrasena; Bambang Permono
MEDICINUS Vol. 34 No. 1 (2021): MEDICINUS
Publisher : PT Dexa Medica

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (76.129 KB) | DOI: 10.56951/medicinus.v34i1.49

Abstract

Introduction: Hyperglycemia is a well-known adverse effect of the corticosteroids and asparaginase given during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL). ALL is a type of hematologic malignancy with high incidence in the childhood. The aim of this study is to investigate the impact of hyperglycemia during induction chemotherapy in childhood ALL. Methods: This prospective study was done in Dr. Soetomo hospital from January to April 2018. The subject was newly diagnosed as ALL under the age of 18 years, treated with Indonesian childhood ALL 2013 protocol (standard risk (SR) group and high risk (HR) group). Hyperglycemia was defined as at least two separate random plasma glucose levels >200 mg/dL, which was evaluated before and during induction chemotherapy. Statistical analysis using Paired T-test for parametric and Wilcoxon test for nonparametric. Results: Thirty-three children were enrolled, 18/33 boys with mean age 5.8 (SD 3.78) years, compromised as ALL-L1 30/33. They were treated with ALL-HR 19/33 and ALL-SR 14/33. In overall groups, the mean random blood glucose level significantly increased from 108 (SD 21.3) mg/dl to 147 (SD 48.1) mg/dl, (mean difference 38.67 mg/dl; 95% CI 18.08 to 59.26 mg/dl, p=0.008). In SR group, there was a significant increase of mean random blood glucose level from 102 (SD 13.5) mg/dl to 133 (SD 37.3) mg/dl, (mean difference 31.8 mg/dl; 95% CI 8.78 to 54.8 mg/dl; p=0.01). In HR group, the mean random blood glucose level increased from 113 (SD 51.9) mg/dl to 165 (SD 25.4) mg/dl, (mean difference 51.9 mg/dl; 95% CI 18.6 to 85.2 mg/dl, p=0.004). Conclusion: Blood glucose level is significantly increase during induction chemotherapy in both SR and HR Indonesian childhood ALL 2013 protocol.