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dc.contributor.authorLhermitte, Ludovic-
dc.contributor.authorMejstrikova, Ester-
dc.contributor.authorSluijs-Gelling, Alita J. van der-
dc.contributor.authorGrigore, Georgiana Emilia-
dc.contributor.authorSedek, Lukasz-
dc.contributor.authorBras, A. E.-
dc.contributor.authorGaipa, Giuseppe-
dc.contributor.authorSobral da Costa, E.-
dc.contributor.authorNovákova, Michaela-
dc.contributor.authorSonneveld, Edwin-
dc.contributor.authorBuracchi, Chiara-
dc.contributor.authorBacelar, Thiago S.-
dc.contributor.authorMarvelde, Jeroen G. te-
dc.contributor.authorTrinquand, A.-
dc.contributor.authorAsnafi, V.-
dc.contributor.authorSzczepanski, Tomasz-
dc.contributor.authorMatarraz, Sergio-
dc.contributor.authorLopez, A.-
dc.contributor.authorVidriales, Maria Belén-
dc.contributor.authorBulsa, J.-
dc.contributor.authorHrusak, Ondrej-
dc.contributor.authorKalina, Tomas-
dc.contributor.authorLécrevisse, Quentin-
dc.contributor.authorMartín-Ayuso, Marta-
dc.contributor.authorBrüggemann, Monika-
dc.contributor.authorVerde, J.-
dc.contributor.authorFernandez, P.-
dc.contributor.authorBurgos, Leire-
dc.contributor.authorPaiva, Bruno-
dc.contributor.authorPedreira, C. E.-
dc.contributor.authorDongen, J. J. M. van-
dc.contributor.authorOrfao, Alberto-
dc.contributor.authorVelden, Vincent H. J. van der-
dc.identifierdoi: 10.1038/leu.2017.313-
dc.identifiere-issn: 1476-5551-
dc.identifierissn: 0887-6924-
dc.identifier.citationLeukemia 32(4): 874-881 (2018)-
dc.description.abstractPrecise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications.-
dc.description.sponsorshipThe research was performed within the EuroFlow Consortium, which started with an EU-FP6 grant (LSHB-CT-2006-018708) and obtained sustainability by protecting and licensing intellectual property, thereby obtaining royalties, which are exclusively being used for supporting the EuroFlow research program (chairmen: JJMvD and AO). LS, JB and TS were supported by STRATEGMED3/304586/5/NCBR/2017 PersonALL grant of the Polish National Center for Research and Development. ESC acknowledges FAPERJ, Rio de Janeiro, Brazil (E26/110.105/2014; E26/102.191/2013) and Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPQ of Brazil (400194/2014-7). AO, SM and AL acknowledge the Instituto de Salud Carlos III (MINECO, Madrid, Spain) for the DTS15/00119, and CIBERONC-FEDER-CB16/12/00400 grants. EM, OH, TK and MN were supported by Ministry of Health grant number 15-28525A and NPU LO1604. The research for this manuscript was in part performed within the framework of the Erasmus Postgraduate School Molecular Medicine.-
dc.publisherNature Publishing Group-
dc.relation.isversionofPublisher's version-
dc.titleAutomated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia-
dc.description.versionPeer Reviewed-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderConselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil)-
dc.contributor.funderMinisterio de Sanidad y Consumo (España)-
dc.contributor.funderPolish Academy of Sciences-
dc.contributor.funderFundações de Amparo à Pesquisa (Brasil)-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
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