The role of ß-catenin and paired-like homeobox 2B (PHOX2B) expression in neuroblastoma patients; predictive and prognostic value.

BACKGROUND: The expression of ß-catenin and paired-like homeobox 2B (PHOX2B) expression were assessed in Neuroblastoma (NB) patients as a diagnostic, prognostic and/or predictive markers. METHODS: Bone marrow (BM) samples of 52 NB patients were assessed for the expression of ß-catenin by immunohistochemistry (IHC), and PHOX2B by real time PCR (RT-PCR), compared to 12 healthy normal controls (NC). The data were correlated to the clinic-pathological features of the patients, response to treatment and disease relapse. RESULTS: ß-catenin was expressed in 40 (76.92%) patients (P < .001). While PHOX2B was expressed in 32/52 (61.5%) patients, with a fold change of 0.29 (0.01-40.0, P = .096). ß-catenin expression associated significantly with advanced tumor stage, high risk, positive results by MIBG and bone scan (P = .002, P < .001, P = .006, P = .013; respectively). Also it associated significantly with synaptophysin expression in the BM biopsy (P < .001), with a significant concordance (K = 0.519, P < .001). The expression of ß-catenin associated significantly with PHOX2B gene expression [28/32 (87.5%), P = .04], and its fold change (P = .027), with a significant measure of agreement (K = 0.297, P = .022). The fold change of PHOX2B gene expression associated significantly with the high risk of the patients (P = .04). Poor response to treatment associated significantly with the expression of neuron specific enolase (NSE), ß-catenin and PHOX2B in NB patients (P = .021, P = .019 and P = .040; respectively). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of synaptophysin for the diagnosis of BM metastasis in NB patients were (69%, 65.2%, 71.4%, 62.5%; respectively, P = .024). While with ß-catenin (93.1%, 43.5%, 67.5%, 83.3%; respectively, P = .003), and PHOX2B expression (65.5%, 34.5%, 59.4%, 50%; respectively, P = .574). CONCLUSION: ß-Catenin could be used as a sensitive and reliable marker for detection of BM metastasis and also a good predictor for resistance to treatment in NB patients. While, PHOX2B gene expression in BM aspirate could be a marker for high risk patients and poor response to treatment.

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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Assessment of the Diagnostic Potential of miR-29a-3p and miR-92a-3p as Circulatory Biomarkers in Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a set of Myeloproliferative neoplasms that are identified by excessive growth of myeloid blasts and production of abnormal blood cells. AML is the most common type of acute leukemia that occurs in adults. In addition, AML progresses rapidly and is considered a fatal disease. Thus, there is an urgent need to find new targets for molecularly designed therapies. In This study, we evaluated the circulatory levels of microRNA-29a-3p (miR-29a-3p) and miR-92a-3p beside exploring the expression pattern of their target gene myeloid cell leukemia sequence1 (MCL1) to investigate the role of these molecules in AML pathophysiology and to assess their ability to diagnose AML patients. METHODS: 40 adult AML patients along with 20 healthy subjects were enrolled in this study. Plasma were separated from venous blood samples, collected on EDTA, of all individuals were used to assess circulating miRNAs' levels. In the meantime, total RNA was extracted from isolated leukocytes and was used to quantify target mRNA transcript levels. RESULTS: Our data revealed that the circulating levels of miR-29a-3p and miR-92a-3p exhibited significant reduction in 90% and 100% of AML patients, respectively, when compared to the control group (p<0.001). On the other hand, the transcript level of the target gene of these miRNAs, MCL1, showed a sharp increase in 77.5% (p<0.001) of AML patients, along with a negative correlation with its regulatory miRNAs, miR-29a-3p and miR-92a-3p. CONCLUSION: Our data validates the negative regulatory role of miR-29a-3p and miR-92a-3p to the expression levels of MCL1 in peripheral blood and indicates that these miRNAs can be used as non-invasive diagnostic markers. Furthermore, our study highlights the therapeutic potential of miR-29a-3p and miR-92a-3p to target and downregulate a very important gene (MCL1), which is highly implicated in the pathogenesis of AML.

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.