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Association Between (Gt)N Repeats in Heme Oxygenase-1 Gene Promoter and 3-Year Survival of Patients With Acute Leukemia: A Controlled, Cross-Sectional Study



Kazemi M1, 2, 3 ; Khosravian F3 ; Sameti AA4 ; Moafi A5 ; Merasi MR6 ; Salehi M1, 2, 3 ; Nejati M7 ; Behjati M8
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Authors Affiliations
  1. 1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Medical Genetic Center of Genome, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Isfahan Dental Student Research Committee, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Department of Pediatric Hematology, School of Medicine and Child Health Promotion Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
  7. 7. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
  8. 8. Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

Source: International Journal of Hematology-Oncology and Stem Cell Research Published:2018

Abstract

Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance is remained as the most problematic issue. It is hypothesized that the HO-1 gene up-regulation is responsible for tumor resistance to chemotherapy or radiotherapy-induced apoptosis. HO-1 expression levels are related to (GT)n microsatellite polymorphisms in the location of its promoter.This study designed to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene between acute leukemia patients and healthy controls. Indeed, 3-year disease-free survival was also evaluated. Materials and Methods: Sixty-three patients with acute leukemia and 70 healthy infants were included in this study. We used patient’s medical records to collect data about survival after chemotherapy. The number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer. Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in both cases and controls. Children with longer alleles ((GT)n ≥ 27) had enhanced 3-year survival rate after treatment with chemotherapy or radiotherapy (P<0.05). Conclusion: Although no significant differences were observed between leukemia patients and controls regarding allelic frequency, we found elevated frequency of “LL” genotype in leukemia patients with good prognosis and 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved.
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