2 results on '"Nathalie Grardel"'
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2. Multi-loci diagnosis of acute lymphoblastic leukaemia with high-throughput sequencing and bioinformatics analysis
- Author
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Mikaël Salson, Céline Villenet, Mathieu Giraud, Marc Duez, Claude Preudhomme, Nathalie Grardel, Shéhérazade Sebda, Nicolas Duployez, Yann Ferret, Martin Figeac, Aurélie Caillault, Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, School of Social and Community Medicine [Bristol], University of Bristol [Bristol], Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bioinformatics and Sequence Analysis (BONSAI), Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), SIRIC OncoLille, Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Oncology ,Neoplasm, Residual ,Bioinformatics ,0302 clinical medicine ,hemic and lymphatic diseases ,Diagnosis ,Prospective Studies ,Child ,Paediatric patients ,Sanger sequencing ,V(D)J recombination ,High-Throughput Nucleotide Sequencing ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,3. Good health ,Child, Preschool ,symbols ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Adult ,medicine.medical_specialty ,Bioinformatics analysis ,Adolescent ,High-Throughput Sequencing (HTS) ,Gene Rearrangement, T-Lymphocyte ,Immune Repertoire Sequencing (Rep-Seq) ,DNA sequencing ,03 medical and health sciences ,symbols.namesake ,Young Adult ,Acute Lymphoblastic Leukaemia (ALL) ,Internal medicine ,medicine ,Humans ,Diagnostic Errors ,business.industry ,Infant, Newborn ,Computational Biology ,Infant ,DNA extraction ,Minimal residual disease ,V(D)J Recombination ,Clone Cells ,030104 developmental biology ,Lymphoblastic leukaemia ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,business ,Software ,030215 immunology - Abstract
International audience; High-throughput sequencing (HTS) is considered a technical revolution that has improved our knowledge of lymphoid and autoimmune diseases, changing our approach to leukaemia both at diagnosis and during follow-up. As part of an immunoglobulin/T cell receptor-based minimal residual disease (MRD) assessment of acute lymphoblastic leukaemia patients, we assessed the performance and feasibility of the replacement of the first steps of the approach based on DNA isolation and Sanger sequencing, using a HTS protocol combined with bioinformatics analysis and visualization using the Vidjil software. We prospectively analysed the diagnostic and relapse samples of 34 paediatric patients, thus identifying 125 leukaemic clones with recombinations on multiple loci (TRG, TRD, IGH and IGK), including Dd2/Dd3 and Intron/KDE rearrangements. Sequencing failures were halved (14% vs. 34%, P = 0.0007), enabling more patients to be monitored. Furthermore, more markers per patient could be monitored, reducing the probability of false negative MRD results. The whole analysis, from sample receipt to clinical validation, was shorter than our current diagnostic protocol, with equal resources. V(D)J recombination was successfully assigned by the software, even for unusual recombinations. This study emphasizes the progress that HTS with adapted bioinformatics tools can bring to the diagnosis of leukaemia patients.
- Published
- 2015
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