Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

Frequency of ITPA gene polymorphisms in Iranian patients with acute lymphoblastic leukemia and prediction of its myelosuppressive effects

(2015) Frequency of ITPA gene polymorphisms in Iranian patients with acute lymphoblastic leukemia and prediction of its myelosuppressive effects. LEUKEMIA RESEARCH. pp. 1048-1054.

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Abstract

6-Mercaptopurine (6-MP) plays an important role in treatment of childhood acute lymphoblastic leukemia (ALL). Inosine triphosphate pyrophosphohydrolase (ITPA) is an enzyme involved in 6-MP metabolic pathway that convert the inosine triphosphate (ITP) to inosine monophosphate (IMP) and prevents the accumulation of the toxic metabolite ITP. Our objective was to evaluate the ITPA 94C> A, IVS2+ 21A> C polymorphisms in patients with ALL treated with 6-MP and prediction of its clinical outcomes. Our study population consisted of 70 patients diagnosed with ALL in the Division of Hematology-Oncology of Tehran Mofid Hospital. PCR was carried out to amplify exon 2, exon 3, intron 2, and intron 3 of ITPA gene then, all the amplified fragments were subjected to directional sequencing and then association between genotype and 6-MP toxicity was studied. In this study two exonic variants including 94C> A and 138G> A showed a prevalence of 8.5% and 36.4%, respectively. Two intronic variants, IVS2+ 21A> C and IVS3+101G> A were found in 13.5% and 7% of the samples, respectively. The rate of myelosuppression in the presence of mutant homozygote and heterozygous alleles (94C> A, 138G> A, IVS2+ 21A> C and IVS3+101G> A) was higher than that of wild type alleles during the use of 6-MP. Hepatotoxicity in patients with mutant homozygous and heterozygous 94C> A and IVS3+101G> A during the treatment 6-MP was higher than before treatment with 6-MP. Our results showed that patients with aberrant ITPase genotype (mutant homozygous or heterozygous), more likely to be myelosuppressed and show liver toxicity after treatment with 6-MP. Our results suggest that pre-therapeutic screening of patients for ITPA 94C> A, IVS2+ 21A> C and IVS3+101G> A can help in minimizing the adverse effects of 6-MP in ALL patients. (C) 2015 Elsevier Ltd. All rights reserved.

Item Type: Article
Keywords: Acute lymphoblastic leukemia; Polymorphism; ITPA; 6-MP; Iran
Page Range: pp. 1048-1054
Journal or Publication Title: LEUKEMIA RESEARCH
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q3
Volume: 39
Number: 10
Publisher: web of science,pubmed,scopus
Depositing User: خانم مریم زرقانی
URI: http://repository.zums.ac.ir/id/eprint/2435

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