الفهرس 
Aim of the workOnly 14 pages are availabe for public view
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Abstract
Acute leukemia is an assembly of disorders which are characterized by the accretion of abnormal white cells in the bone marrow, blood and other tissues causing inhibition of blood cell functions. In healthy conditions, it is recognized that there is a subtle balance between the generation of free radicals and antioxidant defense at the cellular level. In some diseases, the free radicals may increase and they produce a challenge to the cellular, morphological and functional integrity of the cell according to their highly reactive nature and may also cause cell death. In this study, we investigated the level of oxidative stress (lipid peroxidation) biomarker malondialdehyde and antioxidant biomarkers, including reduced glutathione level and superoxide dismutase activity in patients with acute leukemia to study the possible consequence of the disease on the level of the oxidative stress and antioxidant activities in the patients. In the field of cancer research, one of the most important requirements is the capacity of biomarkers to permit early characterization of tumors in proportion to their aggressive potential. Tumor biomarkers diagnostic and prognostic value and potential for monitoring efficient therapy regimens have been demonstrated by some clinical trials and they also play a significant role in the pathogenesis of hematopoietic malignancies. With the purpose of fulfilling this aim, the present study deals with the measurement of plasma and leukocytes levels of some cytokine tumor biomarkers, including Cluster of differentiation 137 (CD137) and Tumor necrosis factor receptor 2 (TNFR2), and some tumor invasion biomarkers, including Fascin and Versican and also the determination of the relation of studied markers to the response criteria in selected clinical cases. Additionally, correlations were made between these tumor biomarkers and other studied parameters. This study was carried out on 40 patients with acute leukemia classified into the following two groups: a)group I: consisted of 24 patients with AML with age ranged between 16-66 years with a median of 50 years. This group included 9 females and 15 males. b)group II: consisted of 16 patients with ALL with age ranged between 15-58 years with a median of 25 years. This group included 4 females and 12 males. The control group consisted of 15 apparently healthy subjects with age ranged between 27-50 years with a median of 43 years. This group included 9 females and 6 males. All the patients involved in this study were clinically, radiologically and pathologically examined in the Oncology Centre - Mansoura University. Blood samples were collected from patients before administrating any drug. All patients and control group were subjected to the following investigations: Fasting blood samples were collected in ethylene diamine tetra acetic acid (EDTA) containing tubes. They were divided into two portions: •First portion was used within 5 hours for blood picture investigation and complete blood count was estimated: a. White blood cells count b. Platelets count c. Hemoglobin concentration •Second portion was used for separation of blood components. Then, the following parameters were estimated: 1. In plasma and leukocytes: 1. Cytokine tumor biomarkers: a. Cluster of Differentiation 137 b. Tumor Necrosis Factor Receptor 2. 2. Tumor invasion biomarkers: a. Fascin b. Versican. 2. In leukocytes:Oxidative stress (lipid peroxidation) biomarker: Malondialdehyde (MDA). 3. In hemolysate of RBCs:Antioxidant activity: a. Reduced glutathione (GSH). b. Superoxide dismutase (SOD). The measurements of different biochemical parameters and tumor biomarkers in the patients included in this study reveal the following results: 1. Blood picture: Acute leukemia patients suffered from leukocytosis, anemia and thrombocytopenia. 2. Oxidative damage: Acute leukemia patients showed a significant increase in leukocytes MDA concentration. 3. Antioxidant activity: Acute leukemia patients showed a significant increase in erythrocytes SOD activity. Also, they showed a significant decrease in erythrocytes reduced glutathione concentration. 4. Tumor biomarkers: a. Cytokine tumor biomarkers: Acute leukemia patients (ALL and AML) showed a significant increase in leukocytes CD137 concentration. Also, AML patients who failed to achieve complete remission showed a significant increase in leukocytes CD137 level. ALL patients showed a significant increase in plasma and leukocytes TNFR2 level when compared with the control group and AML patients.b. Tumor invasion biomarkers: AML patients showed a significant increase in the plasma Fascin level when compared with the control group. AML patients showed a significant increase in plasma and leukocytes Versican level when compared with the control group and ALL patients. Also, AML patients who failed to achieve complete remission showed a significant increase in plasma Versican level. Oxidative stress is important in the pathophysiology of many diseases and therefore this explains the interactive relationship between acute leukemia and oxidative stress. Moreover, at the same time, as the leukemic cells are under a continual state of oxidative siege, they produce larger amounts of ROS than non leukemic cells. An increase in the antioxidant activity as an adaptive mechanism is caused by a cascade of events triggered by the increase in free radicals. In leukemic patients, the increase in these antioxidants is not high enough to oppose the dangerous effects of free radicals. Elevated levels of CD137 may be reflective of a specific immune activation stage. Subsequently, CD137 could be considered as an immunoregulatory molecule, which can be expressed ectopically by tumors so as to evade immune surveillance. TNFR2 level in ALL patients is significantly increased as results of patient’s immune system response on tumor and raised TNF production by leukemic cells. Also, increased TNFR2 production reflects an increase in the severity of the disease. Elevated levels of Fascin and Versican in AML patients are associated with cancer relapse and poor patient outcome. When cancer cells invade into extracellular matrix (ECM), they use Fascin to make long filopodia-like protrusions indicating selective Fascin expression in highly metastatic carcinoma cells. Versican is associated with a proliferative cell phenotype and it is often found in tissues showing elevated proliferation such as malignant tumors. Conclusion Firstly, this study declared that the cytokine tumor biomarker CD137 and the tumor invasion biomarker Versican could be potential targets in AML. The cytokines, CD137 and TNFR2, could also act as possible prognostic biomarkers for the outcome of ALL patients. Furthermore, the tumor invasion biomarker Fascin could be a potential biomarker for AML. Lastly, Versican could also be described as a promising biomarker for AML and can be used to distinguish between AML and ALL cases. Further studies are needed for confirmation.