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CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2014; 35(04): 276-280
DOI: 10.4103/0971-5851.144989
ORIGINAL ARTICLE

Thiopurine methyltransferase polymorphisms in children with acute lymphoblastic leukemia

Vijay Gandhi Linga
Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India
,
Dorra Babu Patchva
Department of Pharmacology, Apollo Institute of Medical Science and Reasearch, Hyderabad, Telangana, India
,
Krishna Mohan Mallavarapu Venkata Tulasi
Department of Medical Oncology, Basavatarakam Indo American Cancer Institute and Research, Hyderabad, Telangana, India
,
Krishnamani Iyer Kalpathi
Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India
,
Ashok Pillai
Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India
,
Sadashivudu Gundeti
Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India
,
Senthil J Rajappa
Department of Medical Oncology, Basavatarakam Indo American Cancer Institute and Research, Hyderabad, Telangana, India
,
Raghunadharao Digumarti
Director and Head, Department of Medical Oncology, Tata Memorial Hospital, Aganampudi, Vishakapatnam, Andra Pradesh, India
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Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. 6-mercaptopurine (6-MP) and methotrexate are backbone drugs for maintenance phase of treatment. Purine Analogs 6-MP/6-thioguanine/azathiopurine are metabolized to its inactive form by the enzyme thiopurine methyltransferase (TPMT). Ninety percent of the population harbor wild type on both alleles (TPMT wild/wild), 10% are heterozygous, that is, one allele is mutant (TPMT wild/mutant) and 0.3% are homozygous, that is, both allele are mutant (TPMT mutant/mutant). In heterozygous and homozygous variant, activity of enzyme is low, leading to a higher incidence of toxicity (myelosuppression). Aim: The primary objective was to access the polymorphism of the enzyme, TPMT, in Children with ALL. Secondary objective was to correlate TPMT genotype with 6-MP toxicities. Materials and Methods: Seventy-two children with newly diagnosed ALL during first maintenance phase were serially enrolled after obtaining consent. Five ml of peripheral blood was drawn and DNA extracted. TPMT 2 polymorphisms were performed using Allele specific polymerase chain reaction (PCR) and TPMT 3B and 3C are performed by PCR-restriction fragment length polymorphism. Results: Sixty-nine children of 72 (95.8%) were wild for TPMT polymorphism and 3 (4.2%) were heterozygous for TPMT. Among the heterozygous variant one each (33.3%) were heterozygous for 2A, 3A, 3C. Febrile neutropenia was the most common toxicity in both wild and heterozygous group. Conclusion: The frequency of TPMT polymorphisms in children with ALL is 4.2%. Heterozygous variant is this study are one each (33%) of 2A, 3A, 3C.

Keywords

Acute lymphoblastic leukemia - thiopurine methyltransferase - myelosuppression


Publication History

Article published online:
19 July 2021

© 2014. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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