Comparison of inosine triphosphate pyrophosphatase gene expression in chronic myelogenous leukemia patients and controls

One of the most significant damages to the genetic material is oxidative deamination of DNA and free nucleotides in the cell pool. Incorporation of deaminated purine nucleotides such as inosine triphosphate (ITP, dITP) into the DNA can increase the frequency of base substitution mutation. it has been suggested that presence and accumulation of these rough nucleotides can lead to genetic instability which is the perquisite of different types of diseases or cancers. Inosine triphosphate pyrophosphates (ITPase) encoded by ITPA gene, is responsible for protecting the cells by omitting deaminated purines from the free nucleotide pool. The objective of this study was to examine the possible dysfunction of ITPA gene activity as an important factor in genetic background predisposing to chromosomal disorders and malignancies such as CML. ITPA gene expression study performed on 23 CML patients and 21 controls using semi-quantitative RT-PCR technique and the expression level of GAPDH gene was used as an internal control. Unusual variants obtained from cDNA amplification of ITPA gene were cloned. Our results showed a significant reduction of ITPA gene expression in CML patients in comparison to the controls. Two types of transcripts were produced in addition of expected transcript in some samples. One of them had a 123 nucleotide and the other had 77 nucleotide deletions in their open reading frame. Due to decreased expression of ITPA gene; it seems that the function of ITPase is not normal in CML patients. Therefore the altered expression of this gene can be considered as an additive factor for genetic instability in these patients.