Multi-target measurable residual disease assessed by error-corrected sequencing in patients with acute myeloid leukemia: An ALFA study.

Humans Neoplasm, Residual Leukemia, Myeloid, Acute / genetics Female Male Middle Aged Nucleophosmin Adult Aged Mutation High-Throughput Nucleotide Sequencing Young Adult Prognosis DNA Methyltransferase 3A Aged, 80 and over DNA (Cytosine-5-)-Methyltransferases / genetics Adolescent Repressor Proteins / genetics DNA Mutational Analysis

Journal

Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469

Informations de publication

Date de publication:
13 Jun 2024
Historique:
received: 03 04 2024
accepted: 31 05 2024
revised: 29 05 2024
medline: 14 6 2024
pubmed: 14 6 2024
entrez: 13 6 2024
Statut: epublish

Résumé

The evaluation of measurable residual disease (MRD) in acute myeloid leukemia (AML) using comprehensive mutation analysis by next-generation sequencing (NGS) has been investigated in several studies. However controversial results exist regarding the detection of persisting mutations in DNMT3A, TET2, and ASXL1 (DTA). Benchmarking of NGS-MRD taking into account other molecular MRD strategies has to be done. Here, we performed error-corrected-NGS-MRD in 189 patients homogeneously treated in the ALFA-0702 study (NCT00932412). Persistence of non-DTA mutations (HR = 2.23 for RFS and 2.26 for OS), and DTA mutations (HR = 2.16 for OS) were associated with poorer prognosis in multivariate analysis. Persistence of at least two mutations in complete remission (CR) was associated with a higher cumulative incidence of relapse (CIR) (HR = 3.71, p < 0.0001), lower RFS (HR = 3.36, p < 0.0001) and OS (HR = 3.81, p = 0.00023) whereas persistence of only one mutation was not. In 100 analyzable patients, WT1-MRD, but not NGS-MRD, was an independent factor for RFS and OS. In the subset of 67 NPM1 mutated patients, both NPM1 mutation detection (p = 0.0059) and NGS-MRD (p = 0.035) status were associated with CIR. We conclude that detectable NGS-MRD including DTA mutations correlates with unfavorable prognosis in AML. Its integration with alternative MRD strategies in AML management warrants further investigations.

Identifiants

DOI: 10.1038/s41408-024-01078-8 PMID: 38871702
pubmed: 38871702
doi: 10.1038/s41408-024-01078-8
pii: 10.1038/s41408-024-01078-8
doi:

Substances chimiques

Nucleophosmin 117896-08-9
NPM1 protein, human 0
DNA Methyltransferase 3A EC 2.1.1.37
DNMT3A protein, human 0
DNA (Cytosine-5-)-Methyltransferases EC 2.1.1.37
Repressor Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

97

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Pierre Hirsch (P)

Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, SIRIC CURAMUS, Hôpital Saint-Antoine, Service d'Hématologie Biologique, 75012, Paris, France. Pierre.hirsch@aphp.fr.
ORCID: 0009-0005-1973-3444

Jérôme Lambert (J)

Biostatistics and Medical Information Department, Hôpital Saint Louis, Paris, France.
INSERM U1153 - ECSTRRA Team, Hôpital Saint Louis, Paris, France.

Maxime Bucci (M)

Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000, Lille, France.

Caroline Deswarte (C)

Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, SIRIC CURAMUS, Hôpital Saint-Antoine, Service d'Hématologie Biologique, 75012, Paris, France.

Augustin Boudry (A)

Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000, Lille, France.
ORCID: 0000-0002-9154-1085

Juliette Lambert (J)

Service d'Hématologie Clinique, André Mignot Hospital, Le Chesnay, France.

Laurene Fenwarth (L)

Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000, Lille, France.
ORCID: 0000-0003-2808-4843

Jean-Baptiste Micol (JB)

Gustave Roussy, Université Paris-Saclay, Villejuif, France.
ORCID: 0000-0003-0934-294X

Christine Terré (C)

Laboratory of Hematology, André Mignot Hospital, Le Chesnay, France.

Karine Celli-Lebras (K)

ALFA Group, Paris, France.

Xavier Thomas (X)

Lyon Sud, University Hospital, 69495 Pierre-Bénite, Lyon, France.

Hervé Dombret (H)

Département Hématologie et Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, F-75010, Paris, France.

Nicolas Duployez (N)

Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000, Lille, France.
ORCID: 0000-0002-3927-1022

Claude Preudhomme (C)

Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000, Lille, France.

Raphael Itzykson (R)

Département Hématologie et Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, F-75010, Paris, France.
Université Paris Cité, Génomes, biologie cellulaire et thérapeutique U944, INSERM, CNRS, F-75010, Paris, France.

Francois Delhommeau (F)

Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, SIRIC CURAMUS, Hôpital Saint-Antoine, Service d'Hématologie Biologique, 75012, Paris, France.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Multi-target measurable residual disease...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Maladie résiduelle › Multi-target measurable residual disease...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Leucémies › Leucémie myéloïde › Leucémie aigüe myéloïde › Multi-target measurable residual disease...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Multi-target measurable residual disease...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Nucléophosmine › Multi-target measurable residual disease...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Multi-target measurable residual disease...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Multi-target measurable residual disease...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Multi-target measurable residual disease...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Séquençage nucléotidique à haut débit › Multi-target measurable residual disease...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Jeune adulte › Multi-target measurable residual disease...
questionsmedicales.fr › Diagnostic › Pronostic › Multi-target measurable residual disease...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › DNA modification methylases › DNA-Cytosine Methylases › DNA (cytosine-5-)-methyltransferase › DNA methyltransferase 3A › Multi-target measurable residual disease...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Multi-target measurable residual disease...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › DNA modification methylases › DNA-Cytosine Methylases › DNA (cytosine-5-)-methyltransferase › Multi-target measurable residual disease...
questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Multi-target measurable residual disease...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Multi-target measurable residual disease...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Analyse de mutations d'ADN › Multi-target measurable residual disease...