Detection of Thiopurine S-Methyltransferase (TPMT) Polymorphisms TPMT*3A, TPMT*3B and TPMT*3C in Children with Acute Lymphoblastic Leukemia

  • Nawar S. Mohammed Department of Clinical Biochemistry, College of Medicine, University of Baghdad.
  • Manal K. Rasheed Department of Clinical Biochemistry, College of Medicine, University of Baghdad.
  • Hasanein H. Ghali Department of Pediatrics, College of Medicine, University of Baghdad
  • Shaymaa J. Ahmed  Department of Anatomy, College of Medicine, University of Baghdad
Keywords: Acute Lymphoblastic Leukemia, 6-Mercaptopurine, Thiopurine S-methyltransferase, genetic polymorphisms.

Abstract

Background: Thiopurines are essential medications in Acute Lymphoblastic Leukemia (ALL) treatment protocols as anti-cancer agents since long time; however, their use might result in unexpected toxicities in ALL children due to the low thiopurine S-methyltransferase (TPMT) activity, a major enzyme involved in 6- mercaptopurine metabolism, which strongly correlates to the genetic polymorphism of the TPMT gene in those patients.

Objective: To identify the most common TPMT polymorphisms in children with ALL and its frequencies.

Methods: A cross sectional study enrolling eighty-one ALL children receiving mercaptopurine drug during their maintenance course of treatment according to UKALL – 2011 protocol, were enrolled in this study. After DNA extraction from whole blood TPMT genetic polymorphisms were detected by allele-specific multiplex-PCR analysis.

Results: A total of 51 children with allele frequencies of (62.96%) were homozygous for the wild-type allele TPMT*1, 30 children with allelic frequency of (37.03%) were heterozygous for one of the two mutant alleles (TPMT*3A or TPMT*3C) with allele frequencies of 29.62% and 7.4% respectively, while no result was found homozygous for two mutant alleles or TPMT*3B allele.

Conclusions: This is the first study in Iraq to identify the genetic polymorphism of TPMT in a group of ALL children being treated for ALL. The study revealed the presence of TPMT*3A and TPMT*3C genetic polymorphisms among the study sample, no TPMT*3B was identified in the study sample.

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Author Biographies

Nawar S. Mohammed, Department of Clinical Biochemistry, College of Medicine, University of Baghdad.

   BSc, PhD

 

Manal K. Rasheed, Department of Clinical Biochemistry, College of Medicine, University of Baghdad.

BSc, PhD

Hasanein H. Ghali, Department of Pediatrics, College of Medicine, University of Baghdad

FICMS

Shaymaa J. Ahmed , Department of Anatomy, College of Medicine, University of Baghdad

BSc, PhD

Published
2018-12-31
How to Cite
1.
Mohammed N, Rasheed M, Ghali H, Ahmed S. Detection of Thiopurine S-Methyltransferase (TPMT) Polymorphisms TPMT*3A, TPMT*3B and TPMT*3C in Children with Acute Lymphoblastic Leukemia. JFacMedBagdad [Internet]. 31Dec.2018 [cited 26Sep.2020];60(3):166-71. Available from: http://iqjmc.uobaghdad.edu.iq/index.php/19JFacMedBaghdad36/article/view/608