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.

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. The levels of HO-1 expression 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. Methods: Sixty-three patients with acute leukemia and seventy healthy infants were included in this study. We used the medical records of patients to collect information 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.