title: Thiopurine methyltransferase polymorphisms in children with acute lymphoblastic leukemia.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India.
authors.forename: Vijay Gandhi
authors.initials: VG
authors.lastname: Linga
authors.affiliation: Department of Pharmacology, Apollo Institute of Medical Science and Reasearch, Hyderabad, Telangana, India.
authors.forename: Dorra Babu
authors.initials: DB
authors.lastname: Patchva
authors.affiliation: Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India.
authors.forename: Krishna Mohan
authors.initials: KM
authors.lastname: Mallavarapu
authors.affiliation: Department of Medical Oncology, Basavatarakam Indo American Cancer Institute and Research, Hyderabad, Telangana, India.
authors.forename: Venkata
authors.initials: V
authors.lastname: Tulasi
authors.affiliation: Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India.
authors.forename: Krishnamani Iyer
authors.initials: KI
authors.lastname: Kalpathi
authors.affiliation: Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Pillai
authors.affiliation: Department of Medical Oncology, Nizams Institute of Medical Science, Hyderabad, Telangana, India.
authors.forename: Sadashivudu
authors.initials: S
authors.lastname: Gundeti
authors.affiliation: Department of Medical Oncology, Basavatarakam Indo American Cancer Institute and Research, Hyderabad, Telangana, India.
authors.forename: Senthil J
authors.initials: SJ
authors.lastname: Rajappa
authors.affiliation: Director and Head, Department of Medical Oncology, Tata Memorial Hospital, Aganampudi, Vishakapatnam, Andra Pradesh, India.
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
keywords: Acute lymphoblastic leukemia; myelosuppression; thiopurine methyltransferase