[Home ] [Archive]    
:: Current Issue :: Search :: Submit an Article ::
:: Volume 14, Issue 1 (2022) ::
Iran J War Public Health 2022, 14(1): 75-81 Back to browse issues page
Impact of Gene Expression of TLR4, TLR7, and TLR9 in Children with Acute Lymphocytic Leukemia in Basrah
R.A. Mustafa1, H.A. Jasim *2, S.Kh. Al-Salait3
1- Department of Microbiology, College of Medicine, University of Basrah, Basrah, Iraq
2- Department of Microbiology, College of Medicine, University of Basrah, Basrah, Iraq , hanadi.jasim@uobasrah.edu.iq
3- Department of Pathology, Al-Zahraa Medical College, University of Basrah, Basrah, Iraq
Abstract:   (155 Views)
Aims: Acute lymphoblastic leukemia (ALL) is the most prevalent malignancy in children, accounting for up to 25% of all malignancies in children under the age of 15. TLRs are associated with the transduction of molecular signals in immune processes such as the production of cytokines, and recognition of specific molecular patterns on the surface of microorganisms, but they are also involved in cancer development. This study was trying to throw light on any possible association of gene expression of TLR4, TLR7, and TLR9 in pediatric patients with ALL.
Materials & Methods: A case-control study was conducted on pediatric patients with ALL who have been admitted to Al-Basra Children Teaching Specialty Hospital. Over a period from September 2020 through June 2021, 62 patients (42 newly diagnosed and 20 relapses) were enrolled, in addition to 60 matched normal control, aged 6 months to 16 years. Three ml of blood was collected from all participants in EDTA tubes used for RNA extraction and then molecular analysis. Gene expression of TLR4, TLR7, and TLR9 was done by Real Time-qPCR and the results were reported as ∆Ct (mean±SD).
Findings: The mean ∆Ct of TLR7 (-5.2200±3.29806) reflects the high expression of the gene being the most highly expressed gene (p<0.001). The mean ∆Ct±SD of TLR7 and TLR9 are high in a newly diagnosed group than relapsed one with no significant differences (p=0.686, and 0.400) respectively, while the mean ∆Ct of TLR4 is higher significantly (p<0.05) in a newly diagnosed group than relapsed one.
Conclusion: TLR4, TLR7, and TLR9 gene expression are higher in ALL patients, whether newly diagnosed or relapsed than in the control group. TLRs expression might be part of the immune-evasion mechanism developed by the malignant cells that play an important role in leukemogenicity and disease progression.
Keywords: Quantitative Real Time PCR [MeSH], Toll-Like Receptors [MeSH], ALL Childhood [MeSH],
Full-Text [PDF 620 kb]   (90 Downloads)    
Article Type: Original Research | Subject: Psychology of Veterans or Handicapped
Received: 2022/03/7 | Accepted: 2022/03/26 | Published: 2022/01/20
* Corresponding Author Address: Department of Microbiology, College of Medicine, Al Bradheia, Al Bradheia st., Basrah, Iraq
1. Chennamadhavuni A, Lyengar V, Shimanovsky A. Leukemia. Unknown city: StatPearls; 2021. []
2. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. [] [DOI:10.1182/blood-2016-03-643544] [PMID]
3. Hansen BA, Wendelbo Ø, Bruserud Ø, Hemsing AL, Mosevoll KA, Reikvam H. Febrile neutropenia in acute leukemia. Epidemiology, etiology, pathophysiology and treatment. Mediterr J Hematol Infect Dis. 2020;12(1):e2020009. [] [DOI:10.4084/mjhid.2020.009] [PMID] [PMCID]
4. Montaño A, Forero-Castro M, Marchena-Mendoza D, Benito R, Hernández-Rivas JM. New challenges in targeting signaling pathways in acute lymphoblastic leukemia by NGS approaches: An update. Cancers (Basel). 2018;10(4):110. [] [DOI:10.3390/cancers10040110] [PMID] [PMCID]
5. Kakaje A, Alhalabi MM, Ghareeb A, Karam B, Mansour B, Zahra B, et al. Rates and trends of childhood acute lymphocytic leukaemia: An epidemiology study. Sci Rep. 2020;10(1):6756. [] [DOI:10.1038/s41598-020-63528-0] [PMID] [PMCID]
6. Khan M, Morshed AA, Ahmed TU, Khan HH, Ahmed AF, Roy S. Platelet indices as markers for remission in ALL during induction of remission: an experience of 52 cases. Bangladesh J Child Health. 2020;44(1):34-9. [] [DOI:10.3329/bjch.v44i1.49685]
7. Badr ZA, AL-Moosawi WN, Ali SK. Evaluation of VEGF-A in relation to childhood acute lymphocytic leukemia in Basrah, Iraq. Iraqi Natl J Med. 202;13(1). []
8. Mustafa RA, Jasim HA, Al-Salait SKA. Quantitative determination of serum level of TLR4, TLR7 and TLR9 in pediatric acute lymphoblastic leukemia (ALL) patients in Basrah, Iraq. Biomed Pharmacol J. 2021;14(4). [] [DOI:10.13005/bpj/2325]
9. Möricke A, Zimmermann M, Reiter A, Gadner H, Odenwald E, Harbott J, et al. Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95. Klin Padiatr. 2005;217(6):310-20. [] [DOI:10.1055/s-2005-872515] [PMID]
10. Forestier E, Schmiegelow K, Nordic Society of Paediatric Haematology and Oncology NOPHO. The incidence peaks of the childhood acute leukemias reflect specific cytogenetic aberrations. J Pediatr Hematol Oncol. 2006;28(8):486-95. [] [DOI:10.1097/01.mph.0000212972.90877.28] [PMID]
11. Sameer AS, Nissar S. Toll-like receptors (TLRs): Structure, functions, signaling, and role of their polymorphisms in colorectal cancer susceptibility. BioMed Res Int. 2021;2021:1157023. [] [DOI:10.1155/2021/1157023] [PMID] [PMCID]
12. Patra MC, Choi S. Recent progress in the development of toll-like receptor (TLR) antagonists. Expert Opin Ther Pat. 2016;26(6):719-30. [] [DOI:10.1080/13543776.2016.1185415] [PMID]
13. Kagan J. Signaling organelles of the innate immune system. Cell. 2012;151(6):1168-78. [] [DOI:10.1016/j.cell.2012.11.011] [PMID] [PMCID]
14. Brenner AK, Bruserud Ø. Functional toll-like receptors (TLRs) are expressed by a majority of primary human acute myeloid leukemia cells and inducibility of the TLR signaling pathway is associated with a more favorable phenotype. Cancers (Basel). 2019;11(7):973. [] [DOI:10.3390/cancers11070973] [PMID] [PMCID]
15. Sheyhidin I, Nabi G, Hasim A, Zang RP, Ainiwaer J, Ma H, et al. Overexpression of TLR3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma. World J Gastroenterol. 2011;17(32):3745-51 [] [DOI:10.3748/wjg.v17.i32.3745] [PMID] [PMCID]
16. Khodadadi A, Razmkhah M, Eskandari AR, Hosseini A, Habibagahi M, Ghaderi A, et al. IL-23/IL-27 Ratio in Peripheral Blood of Patients with Breast Cancer. Iran J Med Sci. 2014;39(4):350-6. []
17. Jibb LA, Croal L, Wang J, Yuan C, Foster J, Cheung V, et al. Children's experiences of Cancer care: A systematic review and thematic synthesis of qualitative studies. Oncol Nur Forum. 2018;45(4):527-44. [] [DOI:10.1188/18.ONF.527-544] [PMID]
18. Karim Z, Khidhir KG, Ahmed RA, Hassan HA, Karim DO. Leukemia study in Sulaymaniyah Province, Kurdistan, Iraq. Chin Med J. 2016;129(2):244-5. [] [DOI:10.4103/0366-6999.173551] [PMID] [PMCID]
19. Nodell B. Childhood leukemia rates climb in southern Iraq. Unknown city: UW News; 2010 [Cited 2022 Mar 10]. Available from: https://www.washington.edu/news/2010/02/25/childhood-leukemia-rates-climb-in-southern-iraq/. []
20. Hagopian A, Lafta R, Hassan J, Davis S, Mirick D, Takaro T. Trends in childhood leukemia in Basrah, Iraq, 1993-2007. Am J Pub Heal. 2010;100(6):1081-7. [] [DOI:10.2105/AJPH.2009.164236] [PMID] [PMCID]
21. Barrett AJ. Acute myeloid leukaemia and the immune system: Implications for immunotherapy. Br J Haematol. 2020;188(1):147-58. [] [DOI:10.1111/bjh.16310] [PMID]
22. Alzahrani B. The biology of toll-like receptor 9 and its role in cancer. Crit Rev Eukaryot Gene Expr. 2020;30(5):457-74. [] [DOI:10.1615/CritRevEukaryotGeneExpr.2020036214] [PMID]
23. Sanchez-Cuaxospa M, Contreras-Ramos A, Perez-Figueroa E, MedinaSanson A, Jimenez-Hernandez E, Torres-Nava JR. Low expression of Toll-like receptors in peripheral blood mononuclear cells of pediatric patients with acute lymphocytic leukemia. Int J Oncol. 2016;49(2):675-81. [] [DOI:10.3892/ijo.2016.3569] [PMID]
24. Mokhtari Y, Pourbagheri- Sigaroodi A, Zafari P, Bagheri N, Ghaffari S, et al. Toll-like receptors (TLRs): An old family of immune receptors with a new face in cancer pathogenesis. 2021;25(2):639-51. [] [DOI:10.1111/jcmm.16214] [PMID] [PMCID]
25. Ruan M, Thorn K, Liu S, Li S, Yang W, Zhang C. The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma. Int J Oncol. 2014;44(6):2103-10. [] [DOI:10.3892/ijo.2014.2356] [PMID]
26. Schmitt A, Li L, Giannopoulos K, Greiner J, Reinhardt P, Wiesneth M. Quantitative expression of Toll-like receptor-2, -4, and -9 in dendritic cells generated from blasts of patients with acute myeloid leukemia. Transfusion. 2008;48:861-70. [] [DOI:10.1111/j.1537-2995.2007.01616.x] [PMID]
27. Wang JQ, Jeelall YS, Ferguson LL, Horikawa K. Toll-like receptors and cancer: MYD88 mutation and inflammation. Front Immunol. 2014;5:367. [] [DOI:10.3389/fimmu.2014.00367]
28. Pehlivan M, Sahin H, Ozdilli K, Onay H, Ozcan A, Ozkinay F. Gene Polymorphisms and Febrile Neutropenia in Acute Leukemia-No Association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 Are Associated with the Disease in Turkish Patients: A Preliminary Study. Genet Test Mol Biomarks. 2014;18(7). [] [DOI:10.1089/gtmb.2014.0004] [PMID]
29. Chan SL, Mo F, Wong SC, Hui EP, Loong HH, Mok T. The significance of serum interleukin-10 on the outcome of unresectable hepatocellular carcinoma (HCC). J Clin Oncol. 2011;29(4):205. [] [DOI:10.1200/jco.2011.29.4_suppl.205]
30. Park IA, Heo SH, Song IH, Kim YA, Park HS, Bang WSN. Endoplasmic reticulum stress induces secretion of high-mobility group proteins and is associated with tumor-infiltrating lymphocytes in triplenegative breast cancer. Oncotarget. 2016;7(37):59957-64. [] [DOI:10.18632/oncotarget.11010] [PMID] [PMCID]
31. Morais CA, de Rosso VV, Estadella D, Pisani LP. Anthocyanins as inflammatory modulators and the role of the gut microbiota. J Nutr Biochem. 2016;33:1-7. [] [DOI:10.1016/j.jnutbio.2015.11.008] [PMID]
32. Helminen O, Huhta H, Lehenkari PP, Saarnio J, Karttunen TJ, Kauppila JH. Nucleic acid-sensing toll-like receptors 3, 7 and 8 in esophageal epithelium, barrett's esophagus, dysplasia and adenocarcinoma. Oncoimmunology. 2016;5(5):e1127495. [] [DOI:10.1080/2162402X.2015.1127495] [PMID] [PMCID]
33. Cherfils-Vicini J, Platonova S, Gillard M, Laurans L, Validire P, Caliandro R, et al. Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance. J Clin Invest. 2010;120(4):1285-97. [] [DOI:10.1172/JCI36551] [PMID] [PMCID]
34. Webb RN, Cruse JM, Lewis RE. Differential cytokine and Toll-like receptor expression in leukemia. Exp Mol Pathol. 2007;83(3):464-70. [] [DOI:10.1016/j.yexmp.2007.08.011] [PMID]
35. Morsi M, Gharabawy M, Hamed N, El Sawy M, Abou Seada N, Hashad R. Quantitative expression of toll-like receptors TLR-7 and TLR-9 on peripheral blood mononuclear cells in leukemias. J Hematol. 2016;5(1):17-24. [] [DOI:10.14740/jh249w]
36. Han S, Xu W, Wang Z, Qi X, Wang Y, Ni Y. Crosstalk between the HIF-1 and Toll-like receptor/ nuclear factor-ĸB pathways in the oral squamous cell carcinoma microenvironment. Oncotarget. 2016;7:37773-89. [] [DOI:10.18632/oncotarget.9329] [PMID] [PMCID]
37. Basith S, Manavalan B, Yoo TH, Kim SG, Choi S. Roles of toll-like receptors in cancer: A double-edged sword for defense and offense. Arch Pharm Res. 2012;35(8):1297-316. [] [DOI:10.1007/s12272-012-0802-7] [PMID]
38. Rybka J, Butrym A, Wrobel T, Jazwiec B, Stefanko E, Dobrzynska O, et al. The expression of Toll like receptors and development of severe sepsis in patients with acute myeloid leukemias after induction chemotherapy. Med Oncol. 2014;31(12):319. [] [DOI:10.1007/s12032-014-0319-7] [PMID] [PMCID]
39. Pettengill MA, van Haren SD, Li N, Dowling DJ, Bergelson I, Jans J. Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naive B cells. Innate Immun. 2016;22(6):433-43. [] [DOI:10.1177/1753425916651985] [PMID] [PMCID]
40. Ignatz-Hoover JJ, Wang H, Moreton SA, Chakrabarti A, Agarwal MK, Sun K, et al. The role of TLR8 signaling in acute myeloid leukemia differentiation. Leukemia. 2015;29(4):918-26. [] [DOI:10.1038/leu.2014.293] [PMID] [PMCID]
41. Alharbi A, Alshammari W, Alreshidi T. Expressional correlation of Toll-like Receptor 9 (TLR9) with angiogenic factors and anti-apoptotic markers in cervical cancer cells. AIMS Med Sci. 2021;8(1):11-22. [] [DOI:10.3934/medsci.2021002]
42. Smith TJ, Yamamoto K, Kurata M, Yukimori A, Suzuki S, Umeda S. Differential expression of Toll-like receptors in follicular lymphoma, diffuse large B-cell lymphoma and peripheral T-cell lymphoma. Exp Mol Pathol. 2010;89(3):284-90. [] [DOI:10.1016/j.yexmp.2010.08.003] [PMID]
43. Gao C, Kozlowska A, Nechaev S, Li H, Zhang Q, Hossain DMS, et al. TLR9 signaling in the tumor microenvironment initiates cancer recurrence after radiotherapy. Cancer Res. 2013;73(24):7211-21. [] [DOI:10.1158/0008-5472.CAN-13-1314] [PMID] [PMCID]
44. Guerrier T, Youinou P, Pers JO, Jamin C. TLR9 drives the development of transitional B cells towards the marginal zone pathway and promotes autoimmunity. J Autoimmun. 2012;39(3):173-9. [] [DOI:10.1016/j.jaut.2012.05.012] [PMID]
45. Bai L, Chen W, Chen J, Li W, Zhou L, Niu C, et al. Heterogeneity of Toll-like receptor 9 signaling in B cell malignancies and its potential therapeutic application. J Transl Med. 2017;15(1):51. [] [DOI:10.1186/s12967-017-1152-5] [PMID] [PMCID]
46. Al-Kahiry WM, Dammag EA, Abdelsalam HS, Fadlallah HK, Owaist MS. Toll-like receptor 9 negatively related to clinical outcome of AML patients. J Egypt Natl Can Inst. 2020;32: 15. [] [DOI:10.1186/s43046-020-00027-3] [PMID]
Send email to the article author

Add your comments about this article
Your username or Email:


XML     Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mustafa R, Jasim H, Al-Salait S. Impact of Gene Expression of TLR4, TLR7, and TLR9 in Children with Acute Lymphocytic Leukemia in Basrah. Iran J War Public Health. 2022; 14 (1) :75-81
URL: http://ijwph.ir/article-1-1124-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 14, Issue 1 (2022) Back to browse issues page
مجله طب جانباز Iranian Journal of War and Public Health
Persian site map - English site map - Created in 0.05 seconds with 31 queries by YEKTAWEB 4414