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Oncotarget. 2015 Dec 8;6(39):42345-53. doi: 10.18632/oncotarget.5645.

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.

Author information

1
Hematology Department, Lille University Hospital, Lille, France.
2
Hematology Laboratory, Biology and Pathology Center, Lille University Hospital, Lille, France.
3
Hematology Department, Amiens University Hospital, Amiens, France.
4
UMR-S 1172, Team 3, INSERM, Lille, France.
5
Functional Genomic Platform, Cancer Research Institute, Lille, France.
6
Hematology Department, Versailles Hospital, Le Chesnay, France.
7
Hematology Department, Avicenne Hospital, APHP, University Paris 13, Bobigny, France.
8
Hematology Department, CHU de Dijon - Le Bocage Hospital, Dijon, France.
9
Hematology Department, Saint-Louis Hospital, APHP, Paris, France.

Abstract

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.

KEYWORDS:

acute myeloid leukemia; minimal residual disease; next-generation sequencing

PMID:
26486081
PMCID:
PMC4747230
DOI:
10.18632/oncotarget.5645
[Indexed for MEDLINE]
Free PMC Article

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