Estimation of Serum TLR-9,TNF-α, and IL-6 Levels in the Iraqi Patients Diagnosed as Acute Myelogenous Leukemia


  • Maryam Qasim Mohammed Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq.
  • Ali Hussein Alwan Iraq center for cancer and medical genetics research , Mustansiriyah university, Baghdad, Iraq.
  • Asmaa Amer Almukhtar Department of Medical Genetics, Iraqi Center for Cancer and Medical Genetics Research, Mustansiriyah University, Baghdad, Iraq.



Acute Myeloid Leukemia (AML), Toll-Like Receptor-9 (TLR-9), Interleukin-6 (IL-6), Tumor Necrosis Factor Alpha (TNF-α), Tumor Microenvironment (TME), Acute Promyelocytic Leukemia (APL)


Acute myelogenous leukemia (AML) is a varied group of biological and clinical diseases. It is distinguished by the fast proliferation of aberrant cells in the bone marrow, which interferes with normal blood cell formation. Several studies demonstrated that cytokines released by leukemic cells in an autocrine or paracrine manner influence the proliferation of AML cells. Our study aimed to assess serum levels of TLR-9, TNF-α and, IL-6 in patients of AML. The study was done via the ELISA Technique. The results show a highly significant difference in all parameters in Patients and control. The correlation between immunological parameters using the Pearson correlation coefficient for patients showed that there is a weak correlation between TLR-9 and TNF- α, IL-6 with P-values of 0.47 and 0.23 respectively. This may indicate the complex environment of inflammation. However, there was a strong correlation between TNF- α and IL-6 with a P-value (0.001). This indicates that the secretion of these cytokines was high in patients. All immunological parameters of patients were evaluated using the receiver operating characteristic (ROC) curve to demonstrate that any one of them is a useful tool for identifying and tracking inflammation. The ROC curve's findings revealed that all parameters have good sensitivity and specificity for detecting inflammation and disease activity in AML patients. According to the current study, AML was related to higher levels of TLR-9, TNF-α, and, IL-6 may be affected the prognosis of the disease, increase the risk of the disease progression, and may be used as a biomarker to target AML cells.


Lowenberg B, Downing J R, Burnett A. Acute myeloid leukemia. N Engl Med. 1999; 341(14): 1051-1062.‏

Sepehrizadeh Z, Mohammadi M, Emami A, Yazdi M T, Bozchlou S H, Khorramizadeh M R, et al. Assessment of cytokine expression profile in acute myeloid leukemia patients before and after chemotherapy. Turk J Hematol. 2014; 31(2): 149.

Siveen K S, Uddin S, Mohammad R M. Targeting acute myeloid leukemia stem cell signaling by natural products. Mol cancer. 2017; 16: 1-12.‏

Tettamanti S, Pievani A, Biondi A, Dotti G, Serafini M. Catch me if you can: How AML and its niche escape immunotherapy. Leukemia. 2022. 36(1): 13-22.‏

Tahmasebi S, Alimohammadi M, Khorasani S, Rezaei N. Pro-tumorigenic and Anti-tumorigenic Roles of Pro-inflammatory Cytokines in Cancer. In Handbook of Cancer and Immunology. 2022; pp. 1-25. Cham: Springer Int Publishing.‏

Cui X, Zhang H, Cao L, Hu X. Cytokine TNF-α promotes invasion and metastasis of gastric cancer by down-regulating Pentraxin3. J Cancer.2020; 11(7): 1800.‏

Verma S, Singh A, Yadav G, Kushwaha R, Ali W, Verma S. P, et al. Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance. Cureus. 2022; 14(5):e24835.‏

Tian T, Wang M, Ma D. TNF-α, a good or bad factor in hematological diseases?. Stem Cell investig. 2014; 1: 12.

Zhou X, Li Z, Zhou J. Tumor necrosis factor α in the onset and progression of leukemia.Exp Hematol.2017; 45: 17-26.

Cai X, Cao C, Li J, Chen F, Zhang S, Liu B, et al. Inflammatory factor TNF-α promotes the growth of breast cancer via the positive feedback loop of TNFR1/NF-κB (and/or p38)/p-STAT3/HBXIP/TNFR1. Oncotarget. 2017; 8(35): 58338.‏

Kadhum M S, Abdullah A R, Shabeeb Z A. Estimation of the IL-6 serum level in the Iraqi newly diagnosed AML patients.‏ Teikyo Med. J. . 2022; 45(01): 1-5.

Camacho V, Kuznetsova V, Welner R S. Inflammatory cytokines shape an altered immune response during myeloid malignancies. Front Immunol. 2021; 12: 772408.‏

Dawood S D. Assessment of IL-6 serum level in patients with acute myeloid leukemia. Iraqi J Cancer Med Genet. 2011; 4: 22-8.‏

West N R. Coordination of immune-stroma crosstalk by IL-6 family cytokines. Front Immunol. 2019; 10: 1093.‏

Sariani O K, Eghbalpour S, Kazemi E, Buzhani K R, Zaker F. Pathogenic and therapeutic roles of cytokines in acute myeloid leukemia. Cytokine. 2021; 142: 155508.‏

Monlish D A, Bhatt S T, Schuettpelz L G. The role of toll-like receptors in hematopoietic malignancies. Front Immunol. 2016; 7: 390.‏

Fabricius D, Breckerbohm L, Vollmer A, Queudeville M, Eckhoff S M, Fulda S, et al. Acute lymphoblastic leukemia cells treated with CpG oligodeoxynucleotides, IL-4 and CD40 ligand facilitate enhanced anti-leukemic CTL responses. Leukemia. 2011; 25(7): 1111-1121.

George-Gay B, Parker K. Understanding the complete blood count with differential. J Perianesth Nurs. 2003; 18(2): 96-117.

Al-Husseiny A H. Acute myeloid leukemia in adolescent and adult Iraqi patients clinical and hematological study. Diala J. 2008; 29: 1-11.

Ahmed H A, Maklad A M, Khaled S A, Elyamany A. Interleukin-27 and interleukin-35 in de novo acute myeloid leukemia: expression and significance as biological markers. J Blood Med. 2019; 10: 341.‏

Sanchez-Correa B, Bergua J M, Campos C, Gayoso I, Arcos M J, Bañas H, et al. Cytokine profiles in acute myeloid leukemia patients at diagnosis: survival is inversely correlated with IL-6 and directly correlated with IL-10 levels. Cytokine. 2013; 61(3): 885-891.‏

Ahmed H S, Tahir N T, Obed F A. Cytokines profiling as prognostic markers in newly diagnosed acute myeloid leukemia. Iraqi J Hematol.. 2017; 6(2).‏

Tsimberidou A M, Estey E, Wen S, Pierce S, Kantarjian H, Albitar M, et al. The prognostic significance of cytokine levels in newly diagnosed acute myeloid leukemia and high‐risk myelodysplastic syndromes. Cancer. 2008; 113(7): 1605-1613.‏

Wang M, Zhang C, Tian T, Zhang T, Wang R, Han F, et al. Increased regulatory T cells in peripheral blood of acute myeloid leukemia patients rely on the tumor necrosis factor (TNF)-α–TNF receptor-2 pathway. Front Immunol. 2018; 9:1274.‏

Mustafa R A, Jasim H A, Al-Salait S K. A. Quantitative Determination of Serum Level of TLR4, TLR7, and TLR9 in Pediatric Acute Lymphoblastic Leukemia (ALL) Patients in Basrah, Iraq. Biomed Pharma J. 2021; 14(4): 2255-2260.‏

Abdulwahid A G, Abdullah H N. Expression of Serum IL-22, IL-23, and TLR9 as Tumor Markers in Untreated Breast Cancer Patients. Int J Drug Deliv Sci Technol. 2020; 10(03): 472-476.

Ilvesaro J M, Merrell M A, Li L, Wakchoure S, Graves D, Brooks S, et al Toll-like receptor 9 mediates CpG oligonucleotide-induced cellular invasion. Mol Cancer Res. 2008; 6(10): 1534–1543.

Sandholm J, Selander K S. Toll-like receptor 9 in breast cancer. Front Immunol.2014; 5: 330.

Lu C C, Kuo H C, Wang F S, Jou M H, Lee K C, Chuang J H. Upregulation of TLRs and IL-6 as a marker in human colorectal cancer. Int J Mol Sci. 2014; 16(1): 159-177.

Ahmed M F, Salih S M. Impact of Toll-Like Receptors 7 and 9 and Tumor Necrosis Factor-alpha in Iraqi Patients with Urinary Bladder Carcinoma. Int J Drug Deliv Sci Technol. 2021; 11(1): 109-112.,Vol11,Issue1,Article20.pdf

Al-Kahiry W, Dammag E A, Abdelsalam H S, Fadlallah H K, Owais M S. Toll-like receptor 9 is negatively related to the clinical outcome of AML patients. J Egypt Natl Canc Inst.2020; 32(1):1-7.‏

Cytokines and Their Side Effects, online website (2019).

Panezai J, Ghaffar A, Altamash M, Sundqvist KG, Engström P E, Larsson A. Correlation of serum cytokines, chemokines, growth factors, and enzymes with periodontal disease parameters. PloS one.2017;12(11): e0188945.‏





How to Cite

Estimation of Serum TLR-9,TNF-α, and IL-6 Levels in the Iraqi Patients Diagnosed as Acute Myelogenous Leukemia. Baghdad Sci.J [Internet]. [cited 2024 May 28];21(7). Available from: