IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association.
Fiche publication
Date publication
décembre 2015
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHRETIEN Marie-Lorraine
Tous les auteurs :
Debarri H, Lebon D, Roumier C, Cheok M, Marceau-Renaut A, Nibourel O, Geffroy S, Helevaut N, Rousselot P, Gruson B, Gardin C, Chretien ML, Sebda S, Figeac M, Berthon C, Quesnel B, Boissel N, Castaigne S, Dombret H, Renneville A, Preudhomme C
Lien Pubmed
Résumé
Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis.
Mots clés
acute myeloid leukemia, minimal residual disease, next-generation sequencing
Référence
Oncotarget. 2015 Dec 8;6(39):42345-53