المستودع الرقمي العراقي

Iraqi Digital Repository

قياس الفعالية الانزيمية وتحديد الطفرات الجينية لانزيم الثايوبيورين الناقل لمجموع المثيل في عينة من الاطفال العراقيين المصابين بسرطان الدم اللمفاوي الحاد == Thiopurine S - Methyltransferase Phenotype and Genotype in a Sample of Iraqi Children with Acute Lymphoblastic Leukemia

اسم المؤلف: نوار سمير محمد

اسم المشرف: منال كمال رشيد | حسنين حبيب غالي

الموضوع العام: الطب

السنة: 2018

الموضوع الدقيق: الكيمياء الحياتية السريرية

الدرجة: دكتوراه

الجامعة: جامعة بغداد - كلية الطب

اللغة: الانكليزية

مكان الجامعة: بغداد

الصفحات الاولى: 📎 19T1629 - p.pdf

المستخلص: Background : The most common childhood cancer is acute lymphoblastic leukemia which is only treated with chemotherapy alone.All modern protocols of acute lymphoblastic leukemia treatment used thiopurine drugs as an essential anti - cancer drug which used for a long period of time. The 6 - Mercaptopurine is an anti - cancer drug widely used for treating acute lymphoblastic leukemia patients. The patients with low Thiopurine S - Methyltransferase enzyme activity is with an increased risk of developing drug toxicity and consequently unsuccessful acute lymphoblastic leukemia outcome and even death.Thiopurine S - Methyltransferase is one of the main enzymes involved in 6 - mercaptopurine metabolism, and the low activity of this enzyme is strongly correlated to the Thiopurine S - Methyltransferase genetic polymorphism.Aim : Find out the three most common Thiopurine S - Methyltransferase enzyme polymorphism TPMT*3A, TPMT*3B and TPMT*3C in Iraqi pediatric patients with acute lymphoblastic leukemia, and its frequencies. Analyses of Thiopurine S - Methyltransferase activity in the serum of those patients, and compare the results with other population. Methods : This is a cross - sectional study included eighty - one (81) Iraqi pediatric patients with acute lymphoblastic leukemia during the maintenance phase of their UKALL protocol treatment, receiving 6 - Mercaptopurine drug with age range from 1.83 (1year and 10 months) to 16.25 (16 years and 3 months). Thiopurine S - Methyltransferase activity was measured in the patients’ serum by Enzyme - Linked Immunosorbent Assay technique and three of Thiopurine SMethyltransferase genetic polymorphisms were detected by allelespecific multiplex - PCR analysis after DNA extraction from the whole blood. Liver Function Tests were measured by calorimetric method; Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Total Serum Bilirubin in addition to Complete BloodCount measured by automated hematology system. Results : There was significant difference in the mean of Thiopurine S - Methyltransferase activity between pediatric patients carrying the wild - type allele TPMT*1 (n=49), with allele frequencies of 60.4% and pediatric patients (n=32) carrying the mutant alleles (TPMT*3A or TPMT*3C) with allele frequencies of 81.2% and 18.7% respectively. The TPMT*3B allele was not detected in this group. The P - value was highly significant (P<0.000**).Conclusion : This study is the first to analyze Thiopurine SMethyltransferase mutant gene frequency in a sample of the Iraqi population, and it revealed the presence of TPMT*3A and TPMT*3C genetic polymorphism but not a TPMT*3B mutant allele. Thiopurine S - Methyltransferase activity was low in the patients with mutant gene as compared with the wild - type allele patients. Finally, genotype and phenotype of Thiopurine S - Methyltransferase enzyme is an essential predictor to reduce the cytotoxic effects of the anticancer drug and successful acute lymphoblastic leukemia treatment.