title: High-throughput sequencing in acute lymphoblastic leukemia: Follow-up of minimal residual disease and emergence of new clones.
abstract: Minimal residual disease (MRD) is known to be an independent prognostic factor in patients with acute lymphoblastic leukemia (ALL). High-throughput sequencing (HTS) is currently used in routine practice for the diagnosis and follow-up of patients with hematological neoplasms. In this retrospective study, we examined the role of immunoglobulin/T-cell receptor-based MRD in patients with ALL by HTS analysis of immunoglobulin H and/or T-cell receptor gamma chain loci in bone marrow samples from 11 patients with ALL, at diagnosis and during follow-up. We assessed the clinical feasibility of using combined HTS and bioinformatics analysis with interactive visualization using Vidjil software. We discuss the advantages and drawbacks of HTS for monitoring MRD. HTS gives a more complete insight of the leukemic population than conventional real-time quantitative PCR (qPCR), and allows identification of new emerging clones at each time point of the monitoring. Thus, HTS monitoring of Ig/TR based MRD is expected to improve the management of patients with ALL.
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, Inria, UMR 9189 - CRIStAL - Centre de Recherche en Informatique Signal et Automatique de Lille, F-59000 Lille, France. Electronic address: contact@vidjil.org.
authors.forename: Mikaël
authors.initials: M
authors.lastname: Salson
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, Inria, UMR 9189 - CRIStAL - Centre de Recherche en Informatique Signal et Automatique de Lille, F-59000 Lille, France. Electronic address: contact@vidjil.org.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Giraud
authors.affiliation: Univ. Lille, CHU Lille, Department of Hematology, F-59000 Lille, France. Electronic address: aurelie.caillault@chru-lille.fr.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Caillault
authors.affiliation: Univ. Lille, CHU Lille, Department of Hematology, F-59000 Lille, France. Electronic address: nathalie.grardel@chru-lille.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grardel
authors.affiliation: Univ. Lille, CHU Lille, Department of Hematology, F-59000 Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Duployez
authors.affiliation: Univ. Lille, CHU Lille, Department of Hematology, F-59000 Lille, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Ferret
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Duez
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, Inria, UMR 9189 - CRIStAL - Centre de Recherche en Informatique Signal et Automatique de Lille, F-59000 Lille, France.
authors.forename: Ryan
authors.initials: R
authors.lastname: Herbert
authors.affiliation: Univ. Lille, CNRS, Centrale Lille, Inria, UMR 9189 - CRIStAL - Centre de Recherche en Informatique Signal et Automatique de Lille, F-59000 Lille, France.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Rocher
authors.affiliation: Univ. Lille, Plate-forme de génomique fonctionnelle et structurale, F-59000 Lille, France.
authors.forename: Shéhérazade
authors.initials: S
authors.lastname: Sebda
authors.affiliation: Univ. Lille, Plate-forme de génomique fonctionnelle et structurale, F-59000 Lille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Quief
authors.affiliation: Univ. Lille, Plate-forme de génomique fonctionnelle et structurale, F-59000 Lille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Villenet
authors.affiliation: Univ. Lille, Plate-forme de génomique fonctionnelle et structurale, F-59000 Lille, France; Univ. Lille, CHU Lille, Cellule bioinformatique, plateau commun de séquençage, F-59000 Lille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.affiliation: Univ. Lille, CHU Lille, Department of Hematology, F-59000 Lille, France. Electronic address: claude.preudhomme@chru-lille.fr.
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
mesh_terms: D001853:Bone Marrow; D002999:Clone Cells / Q000473:pathology; D005500:Follow-Up Studies; D019675:Genes, T-Cell Receptor gamma; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015166:Monitoring, Immunologic; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics; D012189:Retrospective Studies; D012984:Software
chemical_list: D007143:Immunoglobulin Heavy Chains
keywords: Acute lymphoblastic leukemia; Bioinformatics; Follow-up; Minimal residual disease; Repertoire sequencing