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
-
Mohammad Kazemi
,
Farinaz Khosravian
,
Amir Abbas Sameti
,
Alireza Moafi
,
Mohammad Reza Merasi
,
Mansour Salehi
,
Majid Nejati
,
Mohaddeseh Behjati
Abstract
Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance has 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 have been 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: The study included 63 acute leukemia patients and 70 healthy infants. We used patient’s medical records to collect data regarding the post-chemotherapy survival. 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 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy.
Lo Nigro L. Biology of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2013;35(4):245-52.
Arora RS, Arora B. Acute leukemia in children: A review of the current Indian data. South Asian J Cancer. 2016; 5(3):155-60.
Hunger SP, Raetz EA, Loh ML, et al. Improving outcomes for high-risk ALL: translating new discoveries into clinical care. Pediatr Blood Cancer. 2011;56(6):984-93.
Conter V, Aricò M, Basso G, et al. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia. Leukemia. 2010;24(2):255-64.
Hunger SP, Winick NJ, Sather HN, et al. Therapy of low-risk subsets of childhood acute lymphoblastic leukemia: when do we say enough? Pediatr Blood Cancer. 2005;45(7):876-80.
Aricò M, Conter V, Valsecchi MG, et al. Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study. Haematologica. 2005;90(9):1186-91.
Van Dongen-Melman JE, De Groot A, Van Dongen JJ, et al. Cranial irradiation is the major cause of learning problems in children treated for leukemia and lymphoma: a comparative study. Leukemia. 1997;11(8):1197-200.
Dorantes-Acosta E, Pelayo R. Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity? Bone Marrow Res. 2012; 2012: 406796.
Belson M, Kingsley B, Holmes A. Risk factors for acute leukemia in children: a review. Environ Health Perspect. 2007; 115(1):138-145.
Heasman SA, Zaitseva L, Bowles KM, et al. Protection of acute myeloid leukaemia cells from apoptosis induced by front-line chemotherapeutics is mediated by haem oxygenase-1. Oncotarget. 2011; 2(9):658-668.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29.
Bassan R, Hoelzer D. Modern therapy of acute lymphoblastic leukemia. J Clin Oncol. 2011; 29(5):532-43.
Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol rev. 2006; 86(2):583-650.
Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006; 86(2):583-650.
Kiemer AK, Bildner N, Weber NC, et al. Characterization of heme oxygenase 1 (heat shock protein 32) induction by atrial natriuretic peptide in human endothelial cells. Endocrinology. 2003;144(3):802-12.
Immenschuh S, Ramadori G. Gene regulation of heme oxygenase-1 as a therapeutic target. Biochem Pharmacol. 2000;60(8):1121-8.
Exner M, Minar E, Wagner O, et al. The role of heme oxygenase-1 promoter polymorphisms in human disease. Free Radic Biol Med. 2004;37(8):1097-104.
Salinas M, Diaz R, Abraham NG, et al. Nerve growth factor protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a phosphatidylinositol 3-kinase-dependent manner. J Biol Chem. 2003;278(16):13898-904.
Martin D, Rojo AI, Salinas M, et al. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem. 2004;279(10):8919-29.
Malaguarnera L, Imbesi RM, Scuto A, et al. Prolactin increases HO-1 expression and induces VEGF production in human macrophages. J Cell Biochem. 2004;93(1):197-206.
Lam CW, Getting SJ, Perretti M. In vitro and in vivo induction of heme oxygenase 1 in mouse macrophages following melanocortin receptor activation. J Immunol. 2005;174(4):2297-304.
Fang J, Akaike T, Maeda H. Antiapoptotic role of heme oxygenase (HO) and the potential of HO as a target in anticancer treatment. Apoptosis. 2004;9(1):27-35.
Mayerhofer M, Florian S, Krauth MT, et al. Identification of heme oxygenase-1 as a novel BCR/ABL-dependent survival factor in chronic myeloid leukemia. Cancer Res. 2004;64(9):3148-54.
Jozkowicz A, Was H, Dulak J. Heme oxygenase-1 in tumors: is it a false friend? Antioxid Redox Signal. 2007;9(12):2099-117.
Yajima T, Ochiai H, Uchiyama T, et al. Resistance to cytotoxic chemotherapy-induced apoptosis in side population cells of human oral squamous cell carcinoma cell line Ho-1-N-1. Int J Oncol. 2009;35(2):273-80.
Tang D, Tang WJ, Shi XL, et al. Association of the microsatellite (GT) n repeat polymorphisms of the HO-1 gene promoter and corresponding serum levels with the risk of laryngeal squamous cell carcinoma. Acta Otolaryngol. 2016; 136(8):806-11.
Køllgaard T, Kornblit B, Petersen J, et al. (GT)n Repeat Polymorphism in Heme Oxygenase-1 (HO-1) Correlates with Clinical Outcome after Myeloablative or Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation. PloS one. 2016;11(12):e0168210.
Rich A, Nordheim A, Wang AH. The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem. 1984;53:791-846.
Naylor LH, Clark EM. d(TG)n.d(CA)n sequences upstream of the rat prolactin gene form Z-DNA and inhibit gene transcription. Nucleic Acids Res. 1990;18(6):1595-601.
Delic J, Onclercq R, Moisan-Coppey M. Inhibition and enhancement of eukaryotic gene expression by potential non-B DNA sequences. Biochem Biophys Res Commun. 1991;181(2):818-26.
Waring GO 3rd, Laibson PR. Keratoplasty in infants and children. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 1977;83(2):283-96.
Sawa T, Mounawar M, Tatemichi M, et al. Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters. Cancer Lett. 2008;269(1):78-84.
Javanmard SH, Keyhanian K, Loghmani P, et al. Association between heme oxygenase-1 gene promoter polymorphisms and metabolic syndrome in Iranians. Mol Biol Rep. 2012; 39(3):3355-60.
Lo SS, Lin SC, Wu CW, et al. Heme oxygenase-1 gene promoter polymorphism is associated with risk of gastric adenocarcinoma and lymphovascular tumor invasion Ann Surg Oncol. 2007;14(8):2250-6.
Berberat PO, Dambrauskas Z, Gulbinas A, et al. Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment. Clin Cancer Res. 2005;11(10):3790-8.
Marinissen MJ, Tanos T, Bolos M, et al. Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor. J Biol Chem. 2006;281(16):11332-46.
Sunamura M, Duda DG, Ghattas MH, et al. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer. Angiogenesis. 2003;6(1):15-24.
Yanagawa T, Omura K, Harada H, et al. Heme oxygenase-1 expression predicts cervical lymph node metastasis of tongue squamous cell carcinomas. Oral Oncol. 2004;40(1):21-7.
Mayerhofer M, Gleixner KV, Mayerhofer J, et al. Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia: a novel approach to overcome resistance against imatinib. Blood. 2008;111(4):2200-10.
Fang J, Sawa T, Akaike T, et al. Enhancement of chemotherapeutic response of tumor cells by a heme oxygenase inhibitor, pegylated zinc protoporphyrin. Int J Cancer. 2004;109(1):1-8.
Nowis D, Legat M, Grzela T, et al. Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity. Oncogene. 2006;25(24):3365-74.
Was H, Sokolowska M, Sierpniowska A, et al. Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in mice. Free Radic Biol Med. 2011;51(9):1717-26.
Ferrando M, Wan X, Meiss R, et al. Heme oxygenase-1 (HO-1) expression in prostate cancer cells modulates the oxidative response in bone cells. PloS One. 2013;8(11):e80315.
Labanca E, De Luca P, Gueron G, et al. Association of HO-1 and BRCA1 is Critical for the Maintenance of Cellular Homeostasis in Prostate Cancer. Mol Cancer Res. 2015; 13(11):1455-64.
Traverso N, Ricciarelli R, Nitti M, et al. Role of Glutathione in Cancer Progression and Chemoresistance. Oxidative Medicine and Cellular Longevity. 2013; 2013.
Chang KW, Lee TC, Yeh WI, et al. Polymorphism in heme oxygenase-1 (HO-1) promoter is related to the risk of oral squamous cell carcinoma occurring on male areca chewers. Br J Cancer. 2004;91(8):1551-5.
| Files | ||
| Issue | Vol 12, No 1 (2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Acute leukemia 3-year survival GT repeats Heme oxygenase-1 gene promoter | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
