الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Leukemia is a cancer of the early blood-forming cells. Acute lymphocytic (or lymphoblastic (ALL) is more comm on in children than in adults. microRNAs (miRNAs) are short noncoding RNAs of ” " ~ " ”21 to 23 nucleotides in length, regulate mRNA expression. miRNA expression patterns have been found to distinguish tumors of different developmental origin, even better than traditional mRNA expression profiling. miRNA has tumor suppressor or oncogenic functions. miRNA may be involved in the pathogenesis of acute lymphoblastic leukemia (ALL). The proteasome ubiquitination and protein breakdown is the most comm on way for cells to get rid of extra proteins. Ubiquitination that is multistep enzymatic process. Ubiquitin combines with target proteins with the help of E1, E2 and E3 then degraded by the proteasome enzyme complex. Glutathiones S-transferases (GST1) are the enzyme family which stimulates reduced glutathione combination to several substrates that leading to detoxification. This study was designed to study miRNA92a, miRNA638 expressions as well as the expression, levels of GST1 and UAE1 in ALL childhood. In addition, evaluation of their prognostic significance and their association with response to treatment. The subjects of this study were divided into four groups: group I (control group): Contained 30 healthy volunteers with age varied from 8 to 12 years with 9.37 ± 1.19 years (16 males and 14 females). group II (Newly diagnosis): 32 newly-diagnosed children with ALL were investigated before the first dose of chemotherapy, the age varied from 8 to 12 years, 9.37 ± 1.19 years (19 males and 13 females). group III (Relapsed): 21 children with relapsed ALL varied from 10 to 13 years, 11.38 ±1.24 years (13 males and 8 females). group IV (Remitted): 18 children with remitted ALL varied from 10 to 13 years, 11.39 ±1.14 years (12 males and 16 females). The following criteria were applied to all cases: 1- Full history taking. 2- Complete clinical examination. 3- Routine laboratory investigations: - Hb level, TLC, Platelet and Blast. 4- Biochemical investigations: - Liver function tests : Serum ALT, AST activities and serum albumin level. - Kidney function tests : Serum urea and creatinine levels. - miRNA92a, miRNA638 gene expression and ratio miRNA92a/ miRNA638 - Glutathione S-transferase (GST1) and ubiquitin activating enzyme (UAE1) gene expressions. - Glutathione S-transferase (GST1) and ubiquitin activating enzyme (UAE1) levels. The results of the present study showed the following: • GST1 level showed a highly significant increase in newly diagnosed, relapsed and remitted groups as compared with control group. • GST1 level decreased significantly in relapsed and remitted group when compared with newly diagnosed group but in relapsed group the level increased significantly than that of remitted group. • UAE1 level showed a highly significant increase in in newly diagnosed, relapsed and remitted groups as compare d with control group. • Level of UAE1 decreased significantly in relapsed group when compared with newly diagnosed group but in relapsed group the level increased significantly than that of remitted group. Also, remitted group showed a highly significant decrease in UAE1 level than that of newly diagnosed group. • GST1 expression was highly significant decrease in relapsed and remitted groups than that of newly diagnosed group. While, showed a highly significant increase in relapsed group when compared with remitted group. • UAE1 expression showed a highly significant decrease in relapsed and remitted groups as compared with newly diagnosed group. In addition to, highly significantly increase in UAE1 expression was observed in relapsed group when compared with remitted group. • miRNA92a showed (1.22, 2.51 folds) decrease in patients with relapsed and remitted respectively when compared with newly diagnosed groups. Also, miRNA92a showed (2.1 folds) increase in patients with relapsed by as compared with the remitted group. • miRNA638 showed (1.35,2.24 folds) decrease in patients with relapsed and remitted respectively when compared with newly diagnosed groups. Also, miRNA638 showed (1.61 folds) increase in patients with relapsed by as compared with the remitted group. • Ratio of miRNA92a / miRNA638 showed a non-significant change between relapsed and remitted groups and between newly diagnosed and remitted groups. Also, relapsed group showed non- significant change with newly diagnosed group. • There was a significant negative correlation between miRNA92a &638 expression and haemoglobin. • There was a negative correlation between miRNA92a & 638 expressions and platelets. • miRNA92a & 638 expressions had a significant positive correlation with leukocytes in patients with ALL. • There was a positive correlation between miRNA92a & 638 expressions and bone marrow blast percentage. • There was a positive significant correlation between GST1 and UAE1 gene expression in newly diagnosed patients. In the relapsed and remitted treatment groups, there was also a strong positive correlation between GST1 and UAE1 gene expression. In newly diagnosed groups, there was a positive significant correlation between GST1 and UAE1 level at the same time. In both the relapsed and remitted treatment groups, there was a negative correlation between GST1 and UAE1 level. GST1 and UAE1 level in control groups were shown to be positively correlated. • A positive significant correlation was found between GST1 level and its gene expression in newly diagnosed groups, as well as in relapsed and remitted treated groups. In addition, in newly diagnosed groups as well as relapsed and remitted treated groups, there was a positive association between UAE1 level and its gene expression. • There was positive significant correlation between miRNA92a and miRNA638 gene expressions in newly diagnosed groups, relapsed and remitted treatment groups. • AUC of GST1 and UAE1 levels were (0.81) but AUC of GST1 and UAE1 gene expression was (0.94). • Sensitivity of level and gene expression of GST1and UAE1 was 100%. • Specificity of GST1 and UAE1 levels were 62 % but GST1 and UAE1 gene expression was 88%. • AUC of miRNA92a gene expression was (0.755) and AUC of miRNA638 gene expression was (0.862). • Sensitivity of miRNA92a was (41.5%) and Sensitivity of miRNA638 was (54.7%). • Specificity of miRNA92a and miRNA638 was 100%. • PPV of miRNA92a and miRNA638 was 100%. • NPV of miRNA92a was (36.7%) and NPV of miRNA638 was (42.9%).