HFE Gene Mutations as Predisposing Factors for Childhood Acute Lymphoblastic Leukaemia in Iraqi Patients
DOI:
https://doi.org/10.32792/utq/utjsci/v11i1.1153Keywords:
Hemochromatosis gene mutation, C282Y, H63D, childhood acute lymphoblastic leukemia.Abstract
Hemochromatosis is a prevalent hereditary disorder that causes excess iron to build up in the body to dangerous levels. Hereditary hemochromatosis, also known as HFE-related hemochromatosis is carried on by changes in the HFE gene. Investigating the gene mutations of the HFE gene is a way to explore the prevalence of this disease. This study aims to determine the association between hemochromatosis HFE gene mutations (C282Y and H63D) and childhood acute lymphoblastic leukaemia in patients at Basra Specialized Hospital for Children and AL-sadder Teaching Hospital in the Basra governance. QIAamp DNA and Blood Mini Kit were used to isolate and identify Human genomic DNA and detect mutations in the HFE gene using the DNA hybridization method. In this study, the absence of the C282Y mutations in both patients and the control group was identified. However, testing DNA-based hybridization experiments revealed low detection levels of the H63D (homozygous, heterozygous) mutations; in only 12.5% of patients. The H63D (only homozygous) mutations were present in 10% of the control group. The association between patients and the control group is considered statistically significant. The HFE gene mutations (C282Y and H63D), originate in acute lymphoblastic leukaemia in childhood, thus, this study recommends complementary investigations to illustrate this case in more detail with more cases of patients and discover the hidden agents underlying these mutations.
Received: 2023-12-20
Revised: 2024-01-26
Accepted: 2024-02-02
References
T. Terwilliger, and M. Abdul-Hay, “Acute lymphoblastic leukemia: a comprehensive review and 2017 update,” Blood Cancer J, vol. 7, no. 6, pp. e577, Jun 30, 2017.
T. D. Buitenkamp, S. Izraeli, M. Zimmermann, E. Forestier, N. A. Heerema, M. M. van den Heuvel-Eibrink, R. Pieters, C. M. Korbijn, L. B. Silverman, K. Schmiegelow, D. C. Liang, K. Horibe, M. Arico, A. Biondi, G. Basso, K. R. Rabin, M. Schrappe, G. Cario, G. Mann, M. Morak, R. Panzer-Grümayer, V. Mondelaers, T. Lammens, H. Cavé, B. Stark, I. Ganmore, A. V. Moorman, A. Vora, S. P. Hunger, C. H. Pui, C. G. Mullighan, A. Manabe, G. Escherich, J. R. Kowalczyk, J. A. Whitlock, and C. M. Zwaan, “Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group,” Blood, vol. 123, no. 1, pp. 70-7, Jan 2, 2014.
E. Furutani, S. Liu, A. Galvin, S. Steltz, M. M. Malsch, S. K. Loveless, L. Mount, J. H. Larson, K. Queenan, A. A. Bertuch, M. D. Fleming, J. M. Gansner, A. E. Geddis, R. Hanna, S. B. Keel, B. W. Lau, J. M. Lipton, R. Lorsbach, T. A. Nakano, A. Vlachos, W. C. Wang, S. M. Davies, E. Weller, K. C. Myers, and A. Shimamura, “Hematologic complications with age in Shwachman-Diamond syndrome,” Blood Adv, vol. 6, no. 1, pp. 297-306, Jan 11, 2022.
M. Swaminathan, S. A. Bannon, M. Routbort, K. Naqvi, T. M. Kadia, K. Takahashi, Y. Alvarado, F. Ravandi-Kashani, K. P. Patel, R. Champlin, H. Kantarjian, L. Strong, and C. D. DiNardo, “Hematologic malignancies and Li-Fraumeni syndrome,” Cold Spring Harb Mol Case Stud, vol. 5, no. 1, Feb, 2019.
A. E. Willis, and T. Lindahl, “DNA ligase I deficiency in Bloom's syndrome,” Nature, vol. 325, no. 6102, pp. 355-7, Jan 22-28, 1987.
P. Shearer, D. Parham, E. Kovnar, L. Kun, B. Rao, T. Lobe, and C. Pratt, “Neurofibromatosis type I and malignancy: review of 32 pediatric cases treated at a single institution,” Med Pediatr Oncol, vol. 22, no. 2, pp. 78-83, 1994.
R. W. Miller, “Relation between cancer and congenital defects: an epidemiologic evaluation,” J Natl Cancer Inst, vol. 40, no. 5, pp. 1079-85, May, 1968.
A. Aureli, B. Marziani, A. Venditti, T. Sconocchia, and G. Sconocchia, “Acute Lymphoblastic Leukemia Immunotherapy Treatment: Now, Next, and Beyond,” Cancers (Basel), vol. 15, no. 13, Jun 26, 2023.
M. Medinger, D. Heim, C. Lengerke, J. P. Halter, and J. R. Passweg, “[Acute lymphoblastic leukemia - diagnosis and therapy],” Ther Umsch, vol. 76, no. 9, pp. 510-515, 2019.
J. Quessada, W. Cuccuini, P. Saultier, M. Loosveld, C. J. Harrison, and M. Lafage-Pochitaloff, “Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge,” Genes (Basel), vol. 12, no. 6, Jun 17, 2021.
F. Shahab, and F. Raziq, “Clinical presentations of acute leukemia,” J Coll Physicians Surg Pak, vol. 24, no. 7, pp. 472-6, Jul, 2014.
T. Patıroğlu, and H. H. Akar, “The Frequency of HLA-A, HLA-B, and HLA-DRB1 Alleles in Patients with Acute Lymphoblastic Leukemia in the Turkish Population: A Case-Control Study,” Turk J Haematol, vol. 33, no. 4, pp. 339-345, Dec 1, 2016.
P. L. Bittencourt, S. A. Palácios, C. A. Couto, E. L. Cançado, F. J. Carrilho, A. A. Laudanna, J. Kalil, L. C. Gayotto, and A. C. Goldberg, “Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis,” Braz J Med Biol Res, vol. 35, no. 3, pp. 329-35, Mar, 2002.
M. S. Katsarou, M. Papasavva, R. Latsi, and N. Drakoulis, “Hemochromatosis: Hereditary hemochromatosis and HFE gene,” Vitam Horm, vol. 110, pp. 201-222, 2019.
P. C. Adams, G. Jeffrey, and J. Ryan, “Haemochromatosis,” Lancet, vol. 401, no. 10390, pp. 1811-1821, May 27, 2023.
M. Vujić, “Molecular basis of HFE-hemochromatosis,” Front Pharmacol, vol. 5, pp. 42, 2014.
J. C. Barton, and R. T. Acton, “HLA-A and -B alleles and haplotypes in hemochromatosis probands with HFE C282Y homozygosity in central Alabama,” BMC Med Genet, vol. 3, pp. 9, Oct 7, 2002.
J. C. Barton, C. Q. Edwards, and R. T. Acton, “HFE gene: Structure, function, mutations, and associated iron abnormalities,” Gene, vol. 574, no. 2, pp. 179-92, Dec 15, 2015.
W. N. Campos, J. D. Massaro, A. L. C. Martinelli, J. A. Halliwell, S. G. E. Marsh, C. T. Mendes-Junior, and E. A. Donadi, “HFE gene polymorphism defined by sequence-based typing of the Brazilian population and a standardized nomenclature for HFE allele sequences,” Hla, vol. 90, no. 4, pp. 238-242, Oct, 2017.
J. N. Feder, A. Gnirke, W. Thomas, Z. Tsuchihashi, D. A. Ruddy, A. Basava, F. Dormishian, R. Domingo, Jr., M. C. Ellis, A. Fullan, L. M. Hinton, N. L. Jones, B. E. Kimmel, G. S. Kronmal, P. Lauer, V. K. Lee, D. B. Loeb, F. A. Mapa, E. McClelland, N. C. Meyer, G. A. Mintier, N. Moeller, T. Moore, E. Morikang, C. E. Prass, L. Quintana, S. M. Starnes, R. C. Schatzman, K. J. Brunke, D. T. Drayna, N. J. Risch, B. R. Bacon, and R. K. Wolff, “A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis,” Nat Genet, vol. 13, no. 4, pp. 399-408, Aug, 1996.
N. T. Milman, F. V. Schioedt, A. E. Junker, and K. Magnussen, “Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect,” Gastroenterology Res, vol. 12, no. 5, pp. 221-232, Oct, 2019.
H. H. Arts, B. Eng, and J. S. Waye, “Multiplex Allele-Specific PCR for Simultaneous Detection of H63D and C282Y HFE Mutations in Hereditary Hemochromatosis,” J Appl Lab Med, vol. 3, no. 1, pp. 10-17, Jul 1, 2018.
F. Zamani, Z. Bagheri, M. Bayat, S. M. Fereshtehnejad, A. Basi, H. Najmabadi, and H. Ajdarkosh, “Iranian hereditary hemochromatosis patients: baseline characteristics, laboratory data and gene mutations,” Med Sci Monit, vol. 18, no. 10, pp. Cr622-9, Oct, 2012.
S. Mubarak, Dhafer, A. Al-Koofee, O. Radhi, A. Radhi, Jawad, J. Ismail, Zubaida, Z. Al-Zubaidi, and D. Al-Koofee, “An Optimization and Common Troubleshooting Solving in Polymerase Chain Reaction Technique,” Systematic Reviews in Pharmacy, vol. 11, pp. 427-436, 03/01, 2020.
M. S. Linet, S. Wacholder, and S. H. Zahm, “Interpreting epidemiologic research: lessons from studies of childhood cancer,” Pediatrics, vol. 112, no. 1 Pt 2, pp. 218-32, Jul, 2003.
A. Gunel-Ozcan, S. Alyilmaz-Bekmez, E. N. Guler, and D. Guc, “HFE H63D mutation frequency shows an increase in Turkish women with breast cancer,” BMC Cancer, vol. 6, pp. 37, Feb 19, 2006.
J. L. Atkins, L. C. Pilling, S. V. Torti, F. M. Torti, G. A. Kuchel, and D. Melzer, “Hereditary Hemochromatosis Variant Associations with Incident Nonliver Malignancies: 11-Year Follow-up in UK Biobank,” Cancer Epidemiol Biomarkers Prev, vol. 31, no. 9, pp. 1780-1787, Sep 2, 2022.
B. Selvaraj, S. Soundararajan, S. Narayanasamy, G. Subramanian, and S. K. Ramanathan, “Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents,” AIMS Molecular Science, vol. 8, no. 4, pp. 233-247, 2021.
J. C. Barton, J. C. Barton, and R. T. Acton, “Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y,” PLoS One, vol. 17, no. 7, pp. e0271973, 2022.
F. H. El-Rashedi, M. A. El-Hawy, S. M. El-Hefnawy, and M. M. Mohammed, “HFE gene mutation and iron overload in Egyptian pediatric acute lymphoblastic leukemia survivors: a single-center study,” Hematology, vol. 22, no. 7, pp. 398-404, Aug, 2017.
Y. F. Lv, X. Chang, R. X. Hua, G. N. Yan, G. Meng, X. Y. Liao, X. Zhang, and Q. N. Guo, “The risk of new-onset cancer associated with HFE C282Y and H63D mutations: evidence from 87,028 participants,” J Cell Mol Med, vol. 20, no. 7, pp. 1219-33, Jul, 2016.
A. Viola, L. Pagano, D. Laudati, R. D'Elia, M. R. D'Amico, M. Ammirabile, S. Palmieri, L. Prossomariti, and F. Ferrara, “HFE gene mutations in patients with acute leukemia,” Leuk Lymphoma, vol. 47, no. 11, pp. 2331-4, Nov, 2006.
M. Schneeweiss-Gleixner, G. Greiner, S. Herndlhofer, J. Schellnegger, M. T. Krauth, K. V. Gleixner, F. Wimazal, C. Steinhauser, M. Kundi, R. Thalhammer, I. Schwarzinger, G. Hoermann, H. Esterbauer, M. Födinger, P. Valent, and W. R. Sperr, “Impact of HFE gene variants on iron overload, overall survival and leukemia-free survival in myelodysplastic syndromes,” Am J Cancer Res, vol. 11, no. 3, pp. 955-967, 2021.
W. R. Gomes, P. P. Devóz, B. A. Rocha, D. Grotto, J. M. Serpeloni, B. L. Batista, A. G. Asimakopoulos, K. Kannan, F. Barbosa Jr., and G. R. M. Barcelos, “Association between Polymorphisms of Hemochromatosis (HFE), Blood Lead (Pb) Levels, and DNA Oxidative Damage in Battery Workers,” International Journal of Environmental Research and Public Health, vol. 20, no. 4, pp. 3513, 2023.
M. A. Al-Tikrity, and M. A. Yassin, “Discrepancy between Serum Ferritin and Liver Iron Concentration in a Patient with Hereditary Hemochromatosis - The Value of T2* MRI,” Case Rep Oncol, vol. 13, no. 2, pp. 712-715, May-Aug, 2020.
Downloads
Published
License
Copyright (c) 2024 University of Thi-Qar Journal of Science
This work is licensed under a Creative Commons Attribution 4.0 International License.
