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

نویسندگان

behrouz hassannia

mehrdad behmanesh

mohammad taghi akbari

چکیده

objective: 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. materials and methods: 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. results: 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. conclusion: 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.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

P-121: Cloning and Expression of The Inosine Triphosphate Pyrophosphatase Gene Variant II in E.coli

Background Environmental and cellular inappropriate conditions can cause damages to cells nucleotide poll. Deamination and oxidation damages interfere with cell�s vital reactions. Inosine triphosphate pyrophosphatase (ITPA), an evolutionary conserved enzyme, plays a critical role in elimination of non-canonical bases. In human genome, the ITPA gene is located on chromosome 20 short arm and tran...

متن کامل

Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin-induced anemia in chronic hepatitis C patients.

Ribavirin (RBV)-induced anemia is a serious side effect of pegylated interferon (PEG-IFN) plus RBV therapy which is the standard care most effective for hepatitis C virus (HCV) infection. In the present study, we investigated the association of inosine triphosphate pyrophosphatase (ITPA) genotypes with RBV-induced hemoglobin (Hb) reduction in HCV patients treated with PEG-IFN/RBV therapy. The g...

متن کامل

Th1 and Th2 Cytokine Gene Polymorphism in Iranian Patients with Chronic Myelogenous Leukemia

Background:It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing Chronic Myelogenous Leukemia (CML). In this regard, Th1 and Th2 cytokines and their gene polymorphism seems to be important. Overall expression and secretion of cytokines is dependent, at least in part, on genetic polymorphism (nucleotide variations) w...

متن کامل

Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene.

ITP and dITP exist in all cells. dITP is potentially mutagenic, and the levels of these nucleotides are controlled by inosine triphosphate pyrophosphatase (EC ). Here we report the cloning, expression, and characterization of a 21.5-kDa human inosine triphosphate pyrophosphatase (hITPase), an enzyme whose activity has been reported in many animal tissues and studied in populations but whose pro...

متن کامل

study of inosine triphosphate pyrophosphohydrolase gene expression in k562 cells

objective: the itpa gene is responsible to remove free deaminated purine nucleotides of itp, ditp and xtp from nucleotide pool of the cells. it seems that dysfunction in its activity, not only can increas the base substitution mutations frequency but also can works as a contrived factor to creating instability in genetic materials of the cells. there are several reports about the existence of s...

متن کامل

Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase.

The structure of human inosine triphosphate pyrophosphohydrolase (ITPA) has been determined using diffraction data to 1.6 A resolution. ITPA contributes to the accurate replication of DNA by cleansing cellular dNTP pools of mutagenic nucleotide purine analogs such as dITP or dXTP. A similar high-resolution unpublished structure has been deposited in the Protein Data Bank from a monoclinic and p...

متن کامل

منابع من

با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید


عنوان ژورنال:
modares journal of medical sciences: pathobiology

ناشر: tarbiat modares university

ISSN 1562-9554

دوره 11

شماره Spring & Summer 2008 2008

میزبانی شده توسط پلتفرم ابری doprax.com

copyright © 2015-2023