|Year : 2017 | Volume
| Issue : 2 | Page : 65-68
Cytokines profiling as prognostic markers in newly diagnosed acute myeloid leukemia
Hiba Shakir Ahmed1, Noor Thair Tahir2, Fatma Abdalhamza Obed3
1 Department of Biology, AL-Karkh University of Science, Baghdad, Iraq
2 Department of Biochemistry, National Diabetic Center, AL-Mustansiriya University, Baghdad, Iraq
3 Department of Cell Separation, Hematological Center, AL-Mustansiriya University, Baghdad, Iraq
|Date of Submission||10-Jun-2017|
|Date of Acceptance||07-Jul-2017|
|Date of Web Publication||9-Oct-2017|
Fatma Abdalhamza Obed
Hematological Center, AL-Mustansiriya University, Baghdad
Source of Support: None, Conflict of Interest: None
Background: Acute myeloid leukemia (AML) is a common acute leukemia in adult. Recent studies have shown that cytokine systems influence leukemic cell biology and clinical investigations. Among various cytokines, interleukin-6 and interleukin-10 (IL-6 and IL-10) participate an essential function in progression of the disease.
Objective: The aim of this study is to quantify of IL-6 and IL-10 levels in AML patients who are newly diagnosed and evaluate lipid profile to assess the relationship between lipid profile level and body mass index (BMI) in myeloid leukemic patients.
Materials And Methods: Samples were collected from 45 patients with AML from AL-Yarmouk Teaching Hospital in addition to another 45 healthy individuals were served as a control group during a period from October 2015 to October 2016. Patients ages ranged from 40 to 60 years. IL-6 and IL-10 were measured in all patients before any treatments and compared with control group.
Results: There was an increase in age, white blood cell, and hemoglobin in AML patients as compared to control, but it was not significant. There was a significant increase in neutrophils and lymphocyte count, (P = 0.001). Furthermore, there was an increase in BMI, fasting blood sugar, and lipid profile except high-density lipoprotein cholesterol for AML patients as compared to control, but it was not significant. There was a significant increase in serum IL-6 and IL-10 for AML patients compared to controls (P = 0.001).
Conclusions: The present study refers that AML patients were associated with high concentration of IL-6 and IL-10 in comparing to the control group.
Keywords: Acute myeloid leukemia, interleukin-10, interleukin-6
|How to cite this article:|
Ahmed HS, Tahir NT, Obed FA. Cytokines profiling as prognostic markers in newly diagnosed acute myeloid leukemia. Iraqi J Hematol 2017;6:65-8
|How to cite this URL:|
Ahmed HS, Tahir NT, Obed FA. Cytokines profiling as prognostic markers in newly diagnosed acute myeloid leukemia. Iraqi J Hematol [serial online] 2017 [cited 2023 Feb 3];6:65-8. Available from: https://www.ijhonline.org/text.asp?2017/6/2/65/216223
| Introduction|| |
Acute myeloid leukemia (AML) is the major frequent type of acute leukemia in adults. Severe infections, resistance, and relapses are the major reasons of death among patients.
It is a clonal disease manifested through the fast proliferation of immature myeloid cells in the bone marrow with an impaired differentiation program. Despite all progress in the therapy of AML and elevated rates of complete remission after induction chemotherapy, many patients will eventually relapse and die from the disease.
This immunosuppressive status might also be accountable for the permanent recurrence of AML and for the failure of immune treatment; a specific connection among immune changes, leukemia immune escape, and infections has not been elucidated. Investigating in this line, reveal that T-helper cells be essential factors with Th17 cells being one of the main and not completely implicated division to date. It has been reported that a potential investigative and predictive is using cytokine levels in recently diagnosed AML as well as myelodysplastic syndromes.
Interleukin-6 (IL-6) is an effective and significant feature for the characteristic enlargement, and the function of T- and B-lymphocytes has great actions on cells of hematopoietic method. IL-6 level in AML patients is improved for inhibitory and stimulatory consequence on clonogenic blast cell growth.
IL-6 is a dominant prognostic factor in chronic lymphocytic leukemia, large cell lymphoma, and diver achieve in the development of AML blast cell, in addition to inspiration and maintenance of their progression throughout the IL-6/IL-6 receptor signaling arrangement.
Interleukin-10 (IL-10) is a homodimer proteins; each of them consists of 178 amino acid, commonly regarded as an anti-inflammatory, and encoded by the IL10 gene, which is located on chromosome 1 and comprises 5 axons.
The aspire of this study was to quantify of IL-6 and IL-10 levels in AML patients who are newly diagnosed and evaluate lipid profile to assess the relationship between lipid profile level and body mass index (BMI) in myeloid leukemic patients.
| Materials and Methods|| |
The blood sample was collected from 45 patients with new diagnosis of AML from AL-Yarmouk Teaching Hospital, in addition to 45 healthy individuals who were considered as a control group.
The period of this study was from October 2015 to October 2016. The cases were diagnosed clinically by consultant hematologist at AL-Yarmouk Teaching Hospital.
The demographic data include age, gender, BMI as well as clinical manifestations, such as bleeding tendency, pallor, bone pain and constitutional symptoms, weakness, respiratory symptoms, organomegaly, and gingival hypertrophy. Hematological parameters were assessed in ethylenediaminetetraacetic acid tube, including white blood cell (WBC), hemoglobin (Hb), neutrophil, and lymphocyte count, were measured and compared between the two groups.
Fasting blood sugar (FBS) and lipid profile, including total cholesterol (TC), triacylglycerol (TAG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C), were determined in both groups using enzymatic colorimetric methods while the concentration of IL-6 and IL-10 were quantitatively determined by enzyme-linked immunosorbent assay using ready kits manufactured by the R and D system. (Bio-techne brand/Minnesota university company/ USA). Finally, the results were estimated.
The statistics were performed by SPSS (Statistical Package of Social Science), version 16 (Chicago, SPSS Inc., USA) program. T-test was used to approximate variances involving both groups in permanent factors. A P < 0.05 was measured to be significantly considerable.
| Results|| |
Clinical manifestations of AML on diagnosis are illustrated in [Table 1]. At diagnosis, most of the patients (31.11%) had fever (n = 14). Anorexia was in (22.22%) while bleeding tendency appears in (17.78%) and pallor in (13.33%).
Demographic, hematological, and biochemical parameters were recorded for all AML patients, as in [Table 2]. There was an increase in age, WBC, and Hb in AML patients as compared to control, but it was not significant.
|Table 2: Hematological and chemical laboratory data for acute myeloid leukemia and control|
Click here to view
There was a significant increase in neutrophils and lymphocyte count (P = 0.001). Furthermore, there was an increase in BMI, FBS, TC, TAG, and LDL-C for AML patients as compared to control, but it was not significant. Distribution of AML according to gender is demonstrated in [Figure 1].
Cytokines profile for AML and control are demonstrated in [Table 3]. There was a significant increase in serum IL-6 and IL-10 for AML patients compared to controls, (P = 0.001).
| Discussion|| |
The hypothesis of coupling the immune system against cancer, including leukemia, has been postulated for very long time, and numerous clinical attempts have been made in this field. Recently, a large evidence from the preclinical and biological view has demonstrated that leukemia cells, including AML, are critically predisposed by the immunological microenvironment, which clearly plays a role in leukemia growth and development. AML can happen during any period; however, the occurrence rises with age. Its significance has developed with an aging population.
As regards age, it was noticed that most patients <60 years. Parallel clarifications were prepared by Yahya et al. when observed that the mean age of the AML patient group was (44.43 ± 10.75) years.
In this study, overall male preponderance was found in this study with a percentage of 55% in males (ratio ≈ 1.5:1). Similar results of gender distribution have been reported in different studies., Main occurrence for all leukemia in males tends to raise as males are comparatively more exposed to work-associated and environmental risks as has been recorded by recent studies.,
WBC count is the mainly imperative risk factor for AML complications. In the present study, WBC count for AML was highest than the control group. This is in agreement with the results of Wetzler et al. This can be demonstrated by the truth that in leukemia there is a clonal proliferation of malignant cells that may arise during any step of maturation in the bone marrow involving myeloid, lymphoid, or pluripotent stages.
Hb level was 10.95 g/dl in AML patients; this is due to the preponderance of patients were anemic with low Hb levels. There was a significant increase in platelet in AML patients as compared to control group, whereas there was a considerable decreased of neutrophil and lymphocyte in those patients as compared to control group, which is accordance with some studies.,
BMI and lipid profile levels in AML patients were not significantly differ from control. This result approved by the study of Rathee et al. This might be interrelated to the high metabolic rate of malignant cells together with the body mass loss that leads to reduce fat substance from cell and so reduce BMI.
Changes in cytokines levels have been associated with autoimmune diseases, allergies, and cancer, involving AML. An inflammatory environment is associated with tumor development and this appears that tumors are dynamic, interacting systems.
The results in this study explained a higher value of IL-6 and IL-10 for de novo AML patients than controls. This result approved by Sanchez-Correa et al.
IL-6 is a pleiotropic cytokine with composite functions in inflammation and metabolic disease. It plays as a proinflammatory cytokine complicated in the acute phase response to tissue injury. It has a causative function in a quantity of inflammatory and autoimmune diseases and its secretion by the adipose tissues participates to metabolic disorder., In addition to its essential function in immune response and inflammatory processes, the function of IL-6 in the angiogenesis, migration, cancer development, and during carcinogenesis is very vital. In many cancer types, IL-6 cannot perform a role in cancer defense; on the contrary, it is concerned in cancer development.
Musuraca et al. noticed that Th17 cells with a double production of IL-10 were closely elevated in AML patients. All exceeding facts maintain the theory that an elevation of IL-10 in AML is a method residential by the disease to generate the immunosuppression status, suggesting that IL-10 could be associated with escape of leukemia cells from immune surveillance.
| Conclusions|| |
The present study refers that AML associated with elevated concentration of IL-6 and IL-10. The improved production of IL-6 and IL-10 in AML patients may stimulate as well as raise the risk of unfavorable prognosis.
The identification of these factors and the clarification of their interaction may ultimately allocate therapeutic intervention in cases of atypical regulation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Estey EH. Acute myeloid leukemia: 2013 update on risk-stratification and management. Am J Hematol 2013;88:318-27.
Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N
Engl J Med 2015;373:1136-52.
Martner A, Thorén FB, Aurelius J, Hellstrand K. Immunotherapeutic strategies for relapse control in acute myeloid leukemia. Blood Rev 2013;27:209-16.
Muranski P, Restifo NP. Essentials of Th17 cell commitment and plasticity. Blood 2013;121:2402-14.
Sanchez-Correa B, Bergua JM, Campos C, Gayoso I, Arcos MJ, 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;61:885-91.
Chen GK, Sale S, Tan T, Ermoian RP, Sikic BI. CCAAT/enhancer-binding protein beta (nuclear factor for interleukin 6) transactivates the human MDR1 gene by interaction with an inverted CCAAT box in human cancer cells. Mol Pharmacol 2004;65:906-16.
Dankbar B, Padró T, Leo R, Feldmann B, Kropff M, Mesters RM, et al.
Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood 2000;95:2630-6.
Elmaksoud N, Raggab HM, El-Latif M. Prognostic impact of elevated serum hyulronic acid, ferritin and interleukin-6 in patients with acute myeloid leukemia. J Am Sci 2010;109:532-41.
Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A, et al
. Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma. Structure 1995;3:591-601.
Mosser DM, Zhang X. Interleukin-10: New perspectives on an old cytokine. Immunol Rev 2008;226:205-18.
Isidori A, Salvestrini V, Ciciarello M, Loscocco F, Visani G, Parisi S, et al.
The role of the immunosuppressive microenvironment in acute myeloid leukemia development and treatment. Expert Rev Hematol 2014;7:807-18.
Wang ES. Treating acute myeloid leukemia in older adults. Hematology Am Soc Hematol Educ Program 2014;2014:14-20.
Yahya DJ, Al-Maaroof ZW, Hassoon AF. Evaluation of leukemia inhibitory factor, interleukin6 and leptin in acute and chronic myeloid leukemia in Babylon Province. Med J Babylon 2016;13:513-21.
Alaa FA, Zedan JZ, Omar SS. Acute myeloid leukemia: Clinical features and follow-up of 115 Iraqi patients admitted to Baghdad teaching hospital, Tikrit. Med J 2009;15:1-8.
Singh G, Parmar P, Kataria SP, Singh S, Sen R. Spectrum of acute and chronic leukemia at a tertiary care hospital, Haryana, India. Int J Res Med Sci 2016;4:1115-8.
Chaudhari S, Desai JS, Adam A, Mishra P. JAK/STAT as a novel target for treatment of leukemia. Int J Pharm Pharm Sci 2014;6:1-7.
Kumar A, Rathee R, Vashist M, Neel Kamal S, Singh S, Gupta S, et al
. Acute lymphocytic leukemia: An epidemiological and hematological study from Haryana. Biosci Biotechnol Res Asia 2012;9:813-7.
Rubnitz JE, Inaba H. Childhood acute myeloid leukaemia. Br J Haematol 2012;159:259-87.
Wetzler M, Byrd JC, Bloomfield CD. Acute and chronic myeloid leukemia. In: Harrison's Principles of Internal Medicine. 18th
ed. London, England: McGraw-Hill; 2012. p. 631-7.
Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, et al.
SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N
Engl J Med 2011;365:2497-506.
Chang F, Shamsi TS, Waryah AM. Clinical and hematological profile of acute myeloid leukemia (AML) patients of Sindh. J Hematol Thromb Dis 2016;4:1-5.
Kupsa T, Vanek J, Vasatova M, Karesova I, Zak P, Jebavy L, et al.
Evaluation of cytokines and soluble adhesion molecules in patients with newly diagnosed acute myeloid leukemia: The role of TNF-alpha and FLT3-ITD. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016;160:94-9.
Rathee R, Vashist M, Kumar A, Singh S. Incidence of acute and chronic forms of leukemia in Haryana. Int J Pharm Pharm Sci 2014;6:323-5.
Kupsa T, Horacek JM, Jebavy L. The role of cytokines in acute myeloid leukemia: A systematic review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012;156:291-301.
Nursal AF, Pehlivan M, Sahin HH, Pehlivan S. The association of IL-6-Y, TNF-α, IL-10 andTGF-β1 Functional variant with Myeloid leukemia in Turkish patients. Genet Test Mol Biomarkers 2016;20:544-51.
Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyen KD, et al.
Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol 2014;15:423-30.
Nagasaki T, Hara M, Nakanishi H, Takahashi H, Sato M, Takeyama H, et al.
Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: Anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction. Br J Cancer 2014;110:469-78.
Musuraca G, De Matteis S, Napolitano R, Papayannidis C, Guadagnuolo V, Fabbri F, et al.
IL-17/IL-10 double-producing T cells: New link between infections, immunosuppression and acute myeloid leukemia. J Transl Med 2015;13:229.
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
||Associations of ficolins and mannose-binding lectin with acute myeloid leukaemia in adults
| ||Anna Sokolowska,Anna S. Swierzko,Gabriela Gajek,Aleksandra Golos,Mateusz Michalski,Mateusz Nowicki,Agnieszka Szala-Pozdziej,Anna Wolska-Washer,Olga Brzezinska,Agnieszka Wierzbowska,Krzysztof Jamroziak,Marek L. Kowalski,Steffen Thiel,Misao Matsushita,Jens C. Jensenius,Maciej Cedzynski |
| ||Scientific Reports. 2020; 10(1) |
|[Pubmed] | [DOI]|