title: Next-generation sequencing of FLT3 internal tandem duplications for minimal residual disease monitoring in acute myeloid leukemia.
abstract: Minimal Residual Disease (MRD) detection can be used for early intervention in relapse, risk stratification, and treatment guidance. FLT3 ITD is the most common mutation found in AML patients with normal karyotype. We evaluated the feasibility of NGS with high coverage (up to 2.4.10(6) PE fragments) for MRD monitoring on FLT3 ITD. We sequenced 37 adult patients at diagnosis and various times of their disease (64 samples) and compared the results with FLT3 ITD ratios measured by fragment analysis. We found that NGS could detect variable insertion sites and lengths in a single test for several patients. We also showed mutational shifts between diagnosis and relapse, with the outgrowth of a clone at relapse different from that dominant at diagnosis. Since NGS is scalable, we were able to adapt sensitivity by increasing the number of reads obtained for follow-up samples, compared to diagnosis samples. This technique could be applied to detect biological relapse before its clinical consequences and to better tailor treatments through the use of FLT3 inhibitors. Larger cohorts should be assessed in order to validate this approach.
authors.affiliation: Laboratory of Hematology, CHRU de Lille, France.|University of Lille Nord de France, Lille, France.
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Bibault
authors.affiliation: Functional and Structural Genomic Platform, Lille, France.|University of Lille Nord de France, Lille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.affiliation: Laboratory of Hematology, CHRU de Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hélevaut
authors.affiliation: Laboratory of Hematology, CHRU de Lille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Rodriguez
authors.affiliation: Functional and Structural Genomic Platform, Lille, France.|Institut Pour la Recherche sur le Cancer de Lille, Lille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Quief
authors.affiliation: Functional and Structural Genomic Platform, Lille, France.|Institut Pour la Recherche sur le Cancer de Lille, Lille, France.
authors.forename: Shéhérazade
authors.initials: S
authors.lastname: Sebda
authors.affiliation: Laboratory of Hematology, CHRU de Lille, France.|University of Lille Nord de France, Lille, France.|Inserm, UMR-S1172, Lille, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
authors.affiliation: Laboratory of Hematology, CHRU de Lille, France.|University of Lille Nord de France, Lille, France.|Inserm, UMR-S1172, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nibourel
authors.affiliation: Department of Hematology, Hôpital de Versailles, Le Chesnay, Université de Versailles-Saint Quentin, Versailles, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.affiliation: Department of Hematology, CHU d'Amiens, Amiens, France.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Gruson
authors.affiliation: Department of Hematology, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Department of Hematology, Hôpital de Versailles, Le Chesnay, Université de Versailles-Saint Quentin, Versailles, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Castaigne
authors.affiliation: Laboratory of Hematology, CHRU de Lille, France.|University of Lille Nord de France, Lille, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction / Q000379:methods; D051941:fms-Like Tyrosine Kinase 3 / Q000737:chemistry / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: FLT3 internal tandem duplication; acute myeloid leukemia; minimal residual disease; next-generation sequencing