Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia
ABSTRACT In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL. Using 12 patient specimens obtained before therapy started, we examined the gene expression profile by oligonucleotide microarrays. We identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of diagnosis accurately distinguished the patients according to disease outcome. These genes are involved in the regulation of apoptosis and cellular proliferation. The prognostic value of the three predictive genes was assessed in an independent cohort of 25 paediatric T-ALL patients using quantitative real-time reverse transcription polymerase chain reaction. Patients assigned to the adverse outcome group had a significantly higher cumulative incidence of relapse compared with patients assigned to the favourable outcome group (46% vs. 8%, P = 0.029). Five-year overall survival was also significantly worse in the patients assigned to the adverse outcome group (P = 0.0039). The independent influence of the 3-gene predictor was confirmed by multivariate analysis. Our study provides proof of principle that genome-wide expression profiling can detect novel molecular prognostic markers in paediatric T-ALL.
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ABSTRACT: Notch signaling plays a critical role in cell fate determination and maintenance of progenitors in many developmental systems. Notch receptors have been shown to be expressed on hematopoietic progenitor cells as well as to various degrees in peripheral blood T and B lymphocytes, monocytes, and neutrophils. Our aim was to understand the protein interaction network, using Notch1 protein name as query in STRING database and we generated a model to assess the significance of Notch1 associated proteins in Acute Lymphoblastic Leukemia (ALL). We further analyzed the expression levels of the genes encoding hub proteins, using Oncomine database, to determine their significance in leukemogenesis. Of the forty two hub genes, we observed that sixteen genes were underexpressed and eleven genes were overexpressed in T-cell Acute Lymphoblastic samples in comparison to their expression levels in normal cells. Of these, we found three novel genes which have not been reported earlier- KAT2B, PSEN1 (underexpressed) and CDH2 (overexpressed).These three identified genes may provide new insights into the abnormal hematopoietic process observed in Leukemia as these genes are involved in Notch signaling and cell adhesion processes. It is evident that experimental validation of the protein interactors in leukemic cells could help in the identification of new diagnostic markers for leukemia.07/2012; 1:e201207005. DOI:10.5936/csbj.201207005
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ABSTRACT: In this paper, we consider tests of correlation when the sample size is much lower than the dimension. We propose a new estimation methodology called the extended cross-data-matrix methodology. By applying the method, we give a new test statistic for high-dimensional correlations. We show that the test statistic is asymptotically normal when p→∞p→∞ and n→∞n→∞. We propose a test procedure along with sample size determination to ensure both prespecified size and power for testing high-dimensional correlations. We further develop a multiple testing procedure to control both family wise error rate and power. Finally, we demonstrate how the test procedures perform in actual data analyses by using two microarray data sets.Journal of Multivariate Analysis 05/2013; 117:313–331. DOI:10.1016/j.jmva.2013.03.007 · 0.94 Impact Factor
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ABSTRACT: We study 1-D photonic crystal in which alternate layers are of materials like chalcogenide As40Se60−xSx and silica. For our three different structures, namely AB, CD and EF in which the refractive index contrast as well as the filling factor is different. Another structure (AB)/(CD)/(EF) which is a combination of earlier multilayer systems has also been considered to study the effect of cascading. Transfer matrix method is used to calculate the omni-directional reflectivity of each multilayer system and omni-directional photonic band gaps (PBGs). We found that large range of omni-directional PBG can be obtained by cascading chalcogenide As40S60−xSex/silica system.Optics Communications 03/2012; 285(6). DOI:10.1016/j.optcom.2011.10.033 · 1.54 Impact Factor