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

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