اسم المؤلف:
هالة فوزي حسن شيشخان الطائي
اسم المشرف:
صفاء عبد الاله فرج | مثنى ابراهيم ملك
الكلمات الدلالية:
- السفينجوسين
- السفينجوسين-1 فوسفات
- p53 , Bcl-2, leukemia
المستخلص:
Leukemia is a blood cancer that usually initiates in the bone marrow and results in high numbers of "abnormal blood cells". Blasts, or leukemia cells, are the term for these immature blood cells. The current study included 80 people, divided into 40 leukemia patients (15 females and 25 males) and 40 healthy individuals (13 females and 27 males) as a control group. The study investigation was done in the College of Science, Department of Biology, University of Wasit, Wasit Governorate, from February 1st, 2021, to January 1st, 2022. Study aimed to evaluate sphingosine and sphingosine -1-phoshate levels, genes (Tnf-α, Bcl-2, and P53), and the correlation between P53, Tnf-α, and Bcl-2 levels and sphingosine and sphingosine -1-phoshate levels and relationship with IL-2 and IL-3 in leukemia patients. This study included hematological tests, biochemical tests, and ELISA tests for Sphingosine, Sphingosine -1-phoshate, IL-2, IL-3 and gene expression (Tnf-α, Bcl-2, and P53) for patients and controls. Biochemical parameters (mean blood urea 0.1, mean serum creatinine, 0.3) and liver function tests measure the concentrations of serum alanine transaminase (ALT) 0.3 liver enzyme and serum aspartate transaminase (AST) 0.01 liver enzyme and total serum bilirubin test TSB 0.03 were detected in four groups of patients and a control group. There was no significant difference (p ≤ 0.05) in the levels of urea and creatinine, while the total serum bilirubin, serum alanine transaminase, and serum aspartate transaminase revealed a substantial rise in patients (p ≤ 0.05) when compared to those of healthy people with a mean SD. Complete Blood Count indices the target records Hematocrit test % 0.001, Hemoglobin concentration g/dl 0.001 and Mean corpuscular hemoglobin pg 0.02 increased significantly, while the parameters (White Blood Cells 0.6 , platelets 0.4 , Mean corpuscular hemoglobin concentration g/dl 0.2, and Mean corpuscular volume f/l 0.08) showed a slight difference, and the levels in the patients did not differ significantly (p ≤ 0.05) when compared with those of healthy people. Sph, S1p, IL2, and IL3 levels were assessed using enzyme-linked immunosorbent assay (ELISA) kits. The results showed an increase in the levels of Sph 0.0001, IL2 0.0001, and IL3 0.0001, with a significant difference and no significant difference in the levels of S1p 0.08. Quantitative real-time qPCR was used to assess Tnf-α, Bcl2, and P53 gene expression in patients when compared to the control group; the results showed a significant increase in P53 0.002 and Bcl 0.02 gene expression but not in Tnf-α 0.5 (p≤ 0.05). In leukemia patients, a correlation study found insignificant relationships (P≤0.05) between gene expression of P53, Tnf-α, Bcl-2, and sphingosine, sphingosine-1-phosphate, IL2, and IL3. This study, found that lipid alteration of sphingosine and sphingosine-1- phosphate has an effect on leukemia patients, especially s1p, which creates a good microenvironment for cell proliferation and inhibits apoptosis. We also found increased interleukin-2,3 in patients, so it is unbalanced, and unbalanced cytokine release contributes to blast proliferation and survival. Also, increased gene expression of Bcl-2 and p53, with a large difference, is a predictor of cancer. Studies have shown that p53 also directly affects Bcl-2 activity. Targeting various signaling pathways is a potential neoteric therapeutic for the treatment of leukemia. Together, Findings demonstrate a critical role for Sphingosine and Sphingosine -1-phosphate in fine-tuning the crosstalk in leukemia patients, thus pointing to the sphingosine and Sphingosine -1-phosphate axes as attractive targets for leukemia treatment.
