Analysis of TNF-α, IL6, IL1-α, IL-10 and TGF-β1 Genes Expression in Acute Myeloid Leukemia Patients in Iranian Patients
Abstract
Acute myeloid leukemia as one of the most common malignant disorders in adults is a heterogeneous clonal disorder of blood producing cells. The aim of this study was to analyze the expression of TNF-α, IL6, IL1-α, IL-10 and TGF-β1 gene in acute myeloid leukemia at diagnosis. The current study was conducted on 50 patients with acute myeloid leukemia and 50 subjects as control group. Serum levels of TNF-α, IL6, IL1-α, IL-10 and TGF-β1 were measured by ELISA. The RNA was extracted, and the expression of TNF-α, IL6, IL1-α, IL-10 and TGF-β1 gene was evaluated using real-time PCR (ΔΔCT computational) after cDNA synthesis. Statistical analysis was performed using Statistical Package for the Social Sciences 19, and P<0.05 was considered as significant level. In patients suffered from acute myeloid leukemia, the mean serum levels of TNF-α, IL6, IL1-α, IL-10 and TGF-β1 were lower than those in the control group. Moreover, the mRNA expression of cytokines in peripheral blood mononuclear cells had a significant decrease in AML patients compared to control group (p<0.0001). The results showed that changes in TNF-α, IL6, IL1-α, IL-10 and TGF-β1 had significant relationship with acute myeloid leukemia. Therefore, the present study supports the use of cytokines as biomarkers in the diagnosis of acute myeloid leukemia.
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2. E.S. Winer, R.M. Stone, “Novel therapy in acute myeloid leukemia (AML): moving toward targeted approaches,” Therapeutic advances in hematology, vol. 10, 2040620719860645, 2019.
3. R.L. Siegel, K.D. Miller, A. Jemal, “Cancer statistics,” CA Cancer J Clin, vol. 68, pp, 7–30, 2018.
4. R.C. Lindsley, B.G. Mar, E. Mazzola, et al, Acute myeloid leukemia ontogeny is defined by distinct somatic mutations, Blood, vol. 125, no. 9, pp.1367–1376, 2015 .
5. E. Papaemmanuil, M. Gerstung, L. Bullinger, et al, Genomic classification and prognosis in acute myeloid leukemia,” N Engl J Med, vol. 374, pp. 2209–2221, 2016.
6. Z. Sepehrizadeh, M. Mohammadi, A. Emami et al, “Assessment of cytokine expression profile in acute myeloid leukemia patients before and after chemotherapy,” Turkish Journal of Hematology, vol. 31, no. 2, p. 149, 2014;
7. J.E. Lancet, J.E Cortes, D.E. Hogge, et al, “Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML,” Blood, vol. 123, no. 21, pp. 3239–3246, 2014.
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9. J.M. Zhang, J. An, “Cytokines, inflammation and pain,” International anesthesiology clinics, vol. 45, no. 2, p. 27, 2007.
10. H. Hassan, A. Zander, “Hematopoietic cytokines in the biology and treatment of acute myeloid leukaemia,” Oncology reports, vol. 4, no. 6, pp.1141-9, 1997.
11. S. Benmerzoug, F.V. Marinho, S. Rose, et al, “GM-CSF targeted immunomodulation affects host response to M. tuberculosis infection,” Scientific reports, vol. 8, no. 1, p. 8652, 2018.
12. V.B. Reddy, D.K. Oelschlager, J.S. Nolan, et al, “Cytokine expression profiles of patients with acute myelogenous leukemia (AML) and non-Hodgkin lymphoma (NHL) detected by multiplex assay,” J ClinOncol ASCO Annual Meeting Proceedings (Post-Meeting Edition), vol. 25, pp. 18530–18530, 2007.
13. X.Z. Gao, S. Bi, H. Copra, et al, “Cytokine gene activity in AML cells in vivo in patients,” Leuk Res, vol. 22, pp. 429–438, 1998.
14. R.C. Bates, A.M. Mercurio, “Tumor necrosis factor-α stimulates the epithelial-to-mesenchymal transition of human colonic organoids,” MolBiol Cell, vol. 14, pp. 1790–1800, 2003;
15. L. Leifeld, S. Cheng, J. Ramakers, et al, “Imbalanced intrahepatic expression of interleukin 12, interferon γ, and interleukin 10 in fulminant hepatitis B,” Hepatology, vol. 36, pp. 1001–1008, 2002.
16. B. Sanchez-Correa, J.M. Bergua, C. Campos, 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, vol. 61, no. 3, pp. 885-91, 2013.
17. D. Langlais, L.B. Barreiro, P. Gros, “The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation,” Journal of Experimental Medicine, vol. 213, no. 4, pp.585-603, 2016.
18. A. Mirzaeian, M.M. Mohammadi, F. Mirzaeyan, B. Chahardouli, S. Rostami, “Investigating the Correlation Between TGF-β Gene Expression and Disease-Related Prognostic Factors in Bone Marrow Aspiration of Adults With Acute Lymphoblastic Leukemia,” ActaMedicaIranica, vol. 56, no.10, p. 640, 2018.
19. M. Dong, G.C. Blobe, “Role of transforming growth factor-β in hematologic malignancies,” Blood. Vol. 107, no.12, pp. 4589-96, 2006.
20. P. Peña-Martínez, M. Eriksson, R. Ramakrishnan, et al, “Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner,” Leukemia, vol. 32, no. 3, p. 588, 2018.
21. H.H. Park, M. Kim, B.H. Lee, J. Lim, Y. Kim, E.J. Lee, W.S. Min, C.S. Kang, W.I. Kim, S.I. Shim, K. Han, “Intracellular IL-4, IL-10, and IFN-γ levels of leukemic cells and bone marrow T cells in acute leukemia,” Annals of Clinical & Laboratory Science, vol. 36, no. 1, pp.7-15, 2006.
22. J. Zhu, H. Yamane, W.E .Paul, “Differentiation of effector CD4 T cell populations,” Annual review of immunology, vol. 28, pp. 445-89, 2009.
23. B.L. Andersen, N.G. Goyal, D.M. Weiss, T.D. Westbrook, K.J. Maddocks, J.C. Byrd, A.J. Johnson, “Cells, cytokines, chemokines, and cancer stress: A biobehavioral study of patients with chronic lymphocytic leukemia,” Cancer, vol. 124, no. 15, pp. 3240-8, 2018.
24. A.K. Brenner, E. Aasebø, M, Hernandez-Valladares, et al, “The Capacity of Long-Term In Vitro Proliferation of Acute Myeloid Leukemia Cells Supported Only by Exogenous Cytokines Is Associated with a Patient Subset with Adverse Outcome,” Cancers, vol. 11, no. 1, p.73, 2019.
| Files | ||
| Issue | Vol 14 No 1 (2022) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v14i1.14388 | |
| Keywords | ||
| Autoimmune disorders Pediatric Leukemia Lymphocytes Hematologic manifestations of systemic diseases | ||
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How to Cite
1.
Ghorbani Ranjbary A, Kajiyazdi M. Analysis of TNF-α, IL6, IL1-α, IL-10 and TGF-β1 Genes Expression in Acute Myeloid Leukemia Patients in Iranian Patients. Basic Clin Cancer Res. 2023;14(1):52-58.
