Genetic Polymorphism of Thiopurine S-Methyltransferase in Children with Acute Lymphoblastic Leukemia
نویسندگان
چکیده
Background: 6-Mercaptopurine (6-MP), a widely used anti-metabolite for the maintenance phase of childhood acute lymphoblastic leukemia (ALL), has been observed to cause myelotoxicity due genetic polymorphism thiopurine methyl transferase (TPMT), one drug-metabolizing enzymes. This study aimed determine frequency S-methyl (TPMT) polymorphic variants in group Pakistani children with (ALL) using 6-mercaptopurine (6-MP). Methods: Diagnosed cases (n=100) ALL, either Pre-B or T Cell, between ages 2 18 years were randomly selected from OPD Children Cancer Hospital and National Institute Child Health (NICH), Karachi. The subjects under BFM (Berlin Frankfurt Munster) protocol. Expired relapsed patients (2/100) excluded. Blood samples drawn DNA was extracted serum genotype TPMT (*2, *3a, *3B *3C) allele-specific PCR (AS-PCR) RFLP. assays done detect G238C transversion TPMT*2 G460A A719G transition TMPT*3 Alleles. Results: Polymorphism TMPT found 100% (98/98) ALL belonging heterozygous group. Out them, 74.5% showed myelotoxicity. Furthermore, *1/*3B most prevalent variant allele highest reported at 97%. *1/*3A only 3 patients, whereas, TMPT*2 *3C Alleles not found. Conclusion: majority our displayed distinct TPMT*1/*3B which is comparatively rare other parts world. Keywords: 6-Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Genetic Polymorphism; Alleles; Pakistan.
منابع مشابه
Genetic Polymorphism of Thiopurine S-methyltransferase in Children with Acute Lymphoblastic Leukemia in Jordan
Background and Aims: It has been demonstrated that homozygote and heterozygote mutant allele carriers for thiopurine S-methyltransferase (TPMT) are at high risk of developing myelosuppression after receiving standard doses of 6-mercaptopurine (6-MP). The aim of this study was to determine the frequency of TPMT deficient alleles in children with acute lymphoblastic leukemia (ALL) in Jordan and t...
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For the past half century, thiopurines have earned themselves a reputation as effective anti-cancer and immunosuppressive drugs. Thiopurine S-methyltransferase (TPMT) is involved in the metabolism of all thiopurines and is one of the main enzymes that inactivates mercaptopurine. 6-MP is now used as a combination therapies for maintenance therapy of children with acute lymphocytic leukemia (A...
متن کاملThiopurine S-methyltransferase phenotype-genotype correlation in children with acute lymphoblastic leukemia.
Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathioprine. TPMT activity exhibits an interindividual variability mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. The a...
متن کاملThiopurine methyltransferase genotyping in Palestinian childhood acute lymphoblastic leukemia patients
BACKGROUND The genetic polymorphism of thiopurine methyltransferase (TPMT) is well characterized in most populations. Four common polymorphic alleles are associated with impaired activity of the enzyme. These are TPMT*2 (238G>C), TPMT*3B (c.460G>A), TPMT*3A (c.460G>A and c.719A>G) and TPMT*3C (c.719A>G). The aim of the present study was to determine the frequency of TPMT polymorphisms and their...
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ژورنال
عنوان ژورنال: Pakistan journal of medicine and dentistry
سال: 2023
ISSN: ['2308-2593', '2313-7371']
DOI: https://doi.org/10.36283/pjmd12-1/003