Expression of microRNA-181a and microRNA-196b in Egyptian Pediatric acute Lymphoblastic Leukemia.

BACKGROUND: Differential expression of miRNA provides important insights into pathogenesis of cancer including leukemia. Deregulation of microRNA may contribute to hematopoietic malignancies. In this study, we aimed to evaluate the role of miR-181a and miR-196b in acute lymphoblastic leukemia (ALL) and correlate their expression with clinical and laboratory data. METHODS: The study was performed on bone marrow samples of 70 consecutive newly diagnosed pediatric (ALL) patients, of which 56 were evaluated for both miR-181a and miR-196b (all 70 for miR-181a) by real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). In addition, bone marrow from seven age and sex matched healthy controls derived from donors of bone marrow transplantation were assessed. RESULTS: miR-181a expression was significantly up-regulated in ALL patients compared with healthy controls (p <0.001). However, miR-196b expression was significantly down-regulated in patients compared with healthy controls (p=0.038). CONCLUSION: Our results suggest that miR-181a has an oncogenic, while miR-196b has a tumor suppressive role in pediatric ALL patients. A finding which demonstrate the potential role of these microRNAs in pathogenesis of pediatric ALL. Also, estimation of their expression level may provide a tool for confirmation of a diagnosis of childhood ALL and could be a possible predictor of early relapse.
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Expression of Micro-RNA 128 and Let-7b in Pediatric Acute Lymphoblastic Leukemia Cases

Background: MicroRNAs (miRNAs) play important roles in the pathogenesis of leukemia and their altered expression is associated with many types of solid and hematological malignancies. Methods: The study was performed on 70 consecutive newly diagnosed pediatric acute lymphoblastic leukemia (ALL) patients, of which 56 were evaluated for both bone marrow miR-128 and let-7b (all 70 for let-7b) by real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). In addition, seven age and sex matched healthy controls were assessed. Results: miR-128 expression was significantly higher in ALL patients compared with healthy controls (p<0.001). However, the expression levels of let-7b showed no statistical significant difference between the groups. No significant links were noted with clinical details, laboratory data and response to treatment. Conclusion: The results suggest that determination of miR-128 expression level may provide a tool for confirmation of a diagnosis of childhood ALL, follow up for response of treatment and a possible predictor of early relapse. Any role of let-7b in pediatric ALL needs to be further assessed.

Association of CYP3A5*3 and CYP1A1*2C Polymorphism with Development of Acute Myeloid Leukemia in Egyptian Patients

Aim: Cytochrome P450 (CYP) enzyme catalyzes the phase I metabolism reaction which metabolize endogenous and exogenous DNA-reactive chemical compounds and xenobiotics which could induce genotoxicity and increase the risk for leukemia. We aimed to detect frequency of CYP3A5*3 and CYP1A1*2C polymorphisms in Egyptian acute myeloid leukemia (AML) patients and to determine role of allele's variants as a risk factor for developing leukemia. Patients and Methods: A case-control study was conducted on seventy acute myeloid leukemia patients and thirty control subjects. Samples were analyzed for prevalence of CYP3A5*3 and CYP1A1*2C polymorphisms using PCR - restriction fragment length polymorphism method. Results: CYP3A5*3 polymorphism (3/3) and (1/3) genotype were significantly elevated in AML group compared to control group (p=0.002). However, no statistical significant differences were found between patients and control group as regard CYP1A1*2C polymorphism. Conclusion: Our results suggest that Egyptians carrying CYP3A5*3 polymorphism might have an increased risk of AML emphasizing the significance of effective phase I detoxification in carcinogenesis.

Relation of BAALC and ERG Gene Expression with Overall Survival in Acute Myeloid Leukemia Cases.

BACKGROUND: The objectives of this study were to evaluate the expression of brain and acute leukemia, cytoplasmic (BAALC) gene and erythroblast transformation-specific related gene (ERG) in de novo cases of acute myeloid leukemia (AML) and identify roles in disease progression and outcome. MATERIALS AND METHODS: This study included 50 newly diagnosed AML patients, along with 10 apparently healthy normal controls. BAALC and ERG expression was detected in the bone marrow of both patients and controls using real-time RT-PCR. RESULTS: BAALC and ERG expression was detected in 52% of cases but not in any controls. There was a statistically significant correlation between BAALC and ERG gene expression and age (p- value=0.004 and 0.019, respectively). No statistical significance was noted for sex, lymphadenopathy, hepatomegaly, splenomegaly, other hematological findings, immunophenotyping and FAB sub-classification except for ERG gene and FAB (p-value=0.058). A statistical significant correlation was found between response to treatment with ERG expression (p-value=0.028) and age (p-value=0.014). A statistically significant variation in overall survival was evident with patient age, BM blast cells, FAB subgroups, BAALC and ERG expression (p-value= <0.001, 0.045, 0.041, <0.008 and 0.025 respectively). CONCLUSIONS: Our results suggest that BAALC and ERG genes are specific significant molecular markers in AML disease progression, response to treatment and survival.