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      Minimal Residual Disease Detection in Acute Lymphoblastic Leukemia

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          Abstract

          Minimal residual disease (MRD) refers to a chemotherapy/radiotherapy-surviving leukemia cell population that gives rise to relapse of the disease. The detection of MRD is critical for predicting the outcome and for selecting the intensity of further treatment strategies. The development of various new diagnostic platforms, including next-generation sequencing (NGS), has introduced significant advances in the sensitivity of MRD diagnostics. Here, we review current methods to diagnose MRD through phenotypic marker patterns or differential gene patterns through analysis by flow cytometry (FCM), polymerase chain reaction (PCR), real-time quantitative polymerase chain reaction (RQ-PCR), reverse transcription polymerase chain reaction (RT-PCR) or NGS. Future advances in clinical procedures will be molded by practical feasibility and patient needs regarding greater diagnostic sensitivity.

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          High-throughput sequencing technologies.

          The human genome sequence has profoundly altered our understanding of biology, human diversity, and disease. The path from the first draft sequence to our nascent era of personal genomes and genomic medicine has been made possible only because of the extraordinary advancements in DNA sequencing technologies over the past 10 years. Here, we discuss commonly used high-throughput sequencing platforms, the growing array of sequencing assays developed around them, as well as the challenges facing current sequencing platforms and their clinical application. Copyright © 2015 Elsevier Inc. All rights reserved.
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            Acute lymphoblastic leukemia: a comprehensive review and 2017 update

            Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL.
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              EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes

              Most consensus leukemia & lymphoma antibody panels consist of lists of markers based on expert opinions, but they have not been validated. Here we present the validated EuroFlow 8-color antibody panels for immunophenotyping of hematological malignancies. The single-tube screening panels and multi-tube classification panels fit into the EuroFlow diagnostic algorithm with entries defined by clinical and laboratory parameters. The panels were constructed in 2–7 sequential design–evaluation–redesign rounds, using novel Infinicyt software tools for multivariate data analysis. Two groups of markers are combined in each 8-color tube: (i) backbone markers to identify distinct cell populations in a sample, and (ii) markers for characterization of specific cell populations. In multi-tube panels, the backbone markers were optimally placed at the same fluorochrome position in every tube, to provide identical multidimensional localization of the target cell population(s). The characterization markers were positioned according to the diagnostic utility of the combined markers. Each proposed antibody combination was tested against reference databases of normal and malignant cells from healthy subjects and WHO-based disease entities, respectively. The EuroFlow studies resulted in validated and flexible 8-color antibody panels for multidimensional identification and characterization of normal and aberrant cells, optimally suited for immunophenotypic screening and classification of hematological malignancies.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                05 February 2020
                February 2020
                : 21
                : 3
                : 1054
                Affiliations
                [1 ]Children’s Hospital Los Angeles, University of Southern California, 4650 Sunset Boulevard, MS #57, Los Angeles, CA 90027, USA; a.kruse@ 123456usc.edu (A.K.); nabdelaz@ 123456usc.edu (N.A.-A.); hyekim@ 123456chla.usc.edu (H.N.K.); yruan@ 123456chla.usc.edu (Y.R.); phanvale@ 123456usc.edu (V.P.); hogana@ 123456chla.usc.edu (H.O.); wsw253@ 123456nyu.edu (W.W.); lee646@ 123456usc.edu (R.L.); ejiang@ 123456chla.usc.edu (E.J.G.)
                [2 ]Department of Pediatrics Patient Care, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; SJKhazal@ 123456mdanderson.org
                Author notes
                [* ]Correspondence: ymkim@ 123456chla.usc.edu
                Author information
                https://orcid.org/0000-0002-3731-608X
                Article
                ijms-21-01054
                10.3390/ijms21031054
                7037356
                32033444
                619bc6f9-35a7-4c4e-a9c9-ab5ceab4753b
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 November 2019
                : 03 February 2020
                Categories
                Review

                Molecular biology
                minimal residual disease,acute lymphoblastic leukemia,b-cell acute lymphoblastic leukemia,t-cell acute lymphoblastic leukemia,flow cytometry,polymerase chain reaction,next-generation sequencing

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