1,720,975 research outputs found

    Computational analysis of flow-cytometry antigen expression profiles in childhood acute lymphoblastic leukemia: an MLL/AF4 identification

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    Precursor B-acute lymphoblastic leukemia (pB-ALL) is a heterogeneous disease and multiparameter flow cytometry, molecular genetics, and cytogenetic studies have all contributed to classification of subgroups with prognostic significance. Recently, gene expression microarray technology has been used to investigate lymphoblastic leukemias, demonstrating that known and novel pB-ALL subclasses can be separated on the basis of gene expression profiles. The strength of microarray technique lays in part in the multivariate nature of the expression data. We propose a parallel multiparametric approach based on immunophenotypic flow-cytometry expression data for the analysis of leukemia patients. Specifically, we tested the potential of this approach on a data set of 145 samples of pediatric pB-ALL that included 46 samples positive for mixed lineage leukemia (MLL) translocations (MLL+) and 99 control pB-ALLs, negative for this translocation ( MLL-). The expression levels of 16 marker proteins have been monitored by four-color flow cytometry using a standardized diagnostic panel of antibodies. The protein expression database has been then analyzed using those univariate and multivariate computational techniques normally applied to mine and model large microarray data sets. Marker protein expression profiling not only allowed separating pB-ALL cases with an MLL rearrangement from other ALLs, but also demonstrates that MLL+ leukemias constitute a heterogeneous group in which MLL/ AF4 leukemias represent a homogenous subclass described by a specific expression fingerprint

    Paediatric palliative care and off-label drug use

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    Paediatric palliative care (PPC) aims to ensure the control of symptoms and the best possible quality of life for patients whose underlying disease, characterised by an unstoppable evolution and negative prognosis, no longer responds to specific treatments. The Italian Medicines Agency (Agenzia Italiana del Farmaco - AIFA) and the Italian Society of Palliative Care (Società Italiana di Cure Palliative - SICP), within a dedicated working group, wrote a document that collects the scientific evidence available to support the offlabel drugs that are more frequently used in adult and PPC. The goal is to certify the consolidated off-label use of these drugs (under the Law 648/96), in the absence of data from its pivotal clinical trials. The paper reports the conditions for this important work and presents the 10 drugs that are usually used off-label in PPC and in pain therapy. At present they are included in Law 648/96 and deemed essential to resolve, at least in part, the unavailability of medicines approved for use in this specific setting

    New methodologic approaches for immunophenotyping acute leukemias

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    Flow cytometry is nowadays the preferred method for immunophenotypic identification, enumeration and characterization of blast cells at diagnosis. Despite widespread application of standardized protocols, inter-laboratory reproducibility has still not been achieved. The complexity of diagnosis and evaluation of minimal residual disease, in immunophenotyping acute leukemia, demands the use of a test that provides all the necessary information

    New methodologic approaches for immunophenotyping acute leukemias

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    BACKGROUND AND OBJECTIVES: Flow cytometry is nowadays the preferred method for immunophenotypic identification, enumeration and characterization of blast cells at diagnosis. Despite widespread application of standardized protocols, inter-laboratory reproducibility has still not been achieved. The complexity of diagnosis and evaluation of minimal residual disease, in immunophenotyping acute leukemia, demands the use of a test that provides all the necessary information. DATA SOURCES AND METHODS: The information given here is derived from the experience of the authors and from literature files. The most relevant studies with adequate conclusions were considered. We report on the current status of multiparametric immunophenotyping using simultaneous three and four-color staining and the applications of this technique. RESULTS: Multiparametric immunophenotyping is a powerful method for achieving a clear discrimination between normal and pathologic cells. The specific identification of leukemic cells by immunologic gating forms the basis for immunophenotypic diagnosis, classification as well as prognostic evaluation of patients with acute leukemias. The performance of the procedure with regards to the panels of reagents and the analytic processes, is necessarily different in lymphoblastic and myeloblastic leukemias, since the diagnostic questions are different. Phenotypic information should be specifically provided for the blast cells and antigen expression should preferably be reported in quantitative units and CV. This would allow a standardized cross evaluation of immunophenotypic results between different investigators and laboratories. INTERPRETATION AND CONCLUSIONS: Recent reports indicate that phenotypic aberrations reflect genetic abnormalities of leukemic cells and therefore their definition and identification is of clinical relevance not only for minimal residual disease monitoring but also for subclassifying acute myeloid and lymphocytic leukemias

    Protein expression profiling of acute lymphoblastic leukemia subclasses.

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    Parallel to fingerprinting of leukemia subclasses by gene expression profiling we propose to fingerprint leukemia subclasses using protein expression data collected by quantitative flow cytometry. A number of acute lymphoblastic leukemia subclasses with characteristic chromosomal aberrations (MLL; Bcr/Abl;E2A/PBX;TEL/AML1;hyperdiploid) have a unique gene expression profile as demonstrated by microarray studies (1-2). Among genes differentially expressed between leukemia subtypes are known proteins of which expression can be measured by quantitative flow cytometry using monoclonal antibodies (3). Here, univariate t-tests and multivariate principal component analysis (PCA) have been applied to profile phenotypes of 145 pB-ALL samples using expression data of 16 proteins. Expression of each marker protein has been quantified in terms of soluble fluorochrome (MESF) and coefficient of variation (CV). Materials:Patients material: A retrospective analysis has been performed on a total of 145 children diagnosed as suffering from precursor-B acute lymphoblastic leukemia (pB-ALL). We included 46 patients that were diagnosed for a MLL rearrangement between May 1995 and June 2001. As a control group representative of pB-ALL’s negative for MLL, we randomly selected 99 consecutively diagnosed patients from our MLL negative reference database.Among MLL patients, 26 are infants (aged < 1 year at diagnosis) and 20 non-infants while in the control group 5 infants (aged < 1 year at diagnosis) and 94 non-infants patients are present

    Computational analysis of flow cytometry antigen expression profiles in childhood acute lymphoblastic leukemia: a MLL/AF4 identification

    No full text
    Precursor B-acute lymphoblastic leukemia (pB-ALL) is a heterogeneous disease and multiparameter flow cytometry, molecular genetics, and cytogenetic studies have all contributed to classification of subgroups with prognostic significance. Recently, gene expression microarray technology has been used to investigate lymphoblastic leukemias, demonstrating that known and novel pB-ALL subclasses can be separated on the basis of gene expression profiles. The strength of microarray technique lays in part in the multivariate nature of the expression data. We propose a parallel multiparametric approach based on immunophenotypic flow-cytometry expression data for the analysis of leukemia patients. Specifically, we tested the potential of this approach on a data set of 145 samples of pediatric pB-ALL that included 46 samples positive for mixed lineage leukemia (MLL) translocations (MLL+) and 99 control pB-ALLs, negative for this translocation (MLL-). The expression levels of 16 marker proteins have been monitored by four-color flow cytometry using a standardized diagnostic panel of antibodies. The protein expression database has been then analyzed using those univariate and multivariate computational techniques normally applied to mine and model large microarray data sets. Marker protein expression profiling not only allowed separating pB-ALL cases with an MLL rearrangement from other ALLs, but also demonstrates that MLL+ leukemias constitute a heterogeneous group in which MLL/AF4 leukemias represent a homogenous subclass described by a specific expression fingerprin

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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