Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.

Journal

Leukemia

ISSN: 1476-5551

Titre abrégé: Leukemia

Pays: England

ID NLM: 8704895

Informations de publication

Date de publication:
04 Jul 2024

Historique:

received: 06 06 2024

accepted: 27 06 2024

revised: 17 06 2024

medline: 5 7 2024

pubmed: 5 7 2024

entrez: 4 7 2024

Statut: aheadofprint

Résumé

Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.

Identifiants

DOI: 10.1038/s41375-024-02333-4 PMID: 38965370

pubmed: 38965370

doi: 10.1038/s41375-024-02333-4

pii: 10.1038/s41375-024-02333-4

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)

ID : CM23/00101

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)

ID : FU 356/12-1

Informations de copyright

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