Clinical impact of the genomic landscape and leukemogenic trajectories in non-intensively treated elderly acute myeloid leukemia patients.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
10
07
2023
accepted:
07
08
2023
revised:
16
07
2023
medline:
6
11
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
To characterize the genomic landscape and leukemogenic pathways of older, newly diagnosed, non-intensively treated patients with AML and to study the clinical implications, comprehensive genetics analyses were performed including targeted DNA sequencing of 263 genes in 604 patients treated in a prospective Phase III clinical trial. Leukemic trajectories were delineated using oncogenetic tree modeling and hierarchical clustering, and prognostic groups were derived from multivariable Cox regression models. Clonal hematopoiesis-related genes (ASXL1, TET2, SRSF2, DNMT3A) were most frequently mutated. The oncogenetic modeling algorithm produced a tree with five branches with ASXL1, DDX41, DNMT3A, TET2, and TP53 emanating from the root suggesting leukemia-initiating events which gave rise to further subbranches with distinct subclones. Unsupervised clustering mirrored the genetic groups identified by the tree model. Multivariable analysis identified FLT3 internal tandem duplications (ITD), SRSF2, and TP53 mutations as poor prognostic factors, while DDX41 mutations exerted an exceptionally favorable effect. Subsequent backwards elimination based on the Akaike information criterion delineated three genetic risk groups: DDX41 mutations (favorable-risk), DDX41
Identifiants
pubmed: 37591941
doi: 10.1038/s41375-023-01999-6
pii: 10.1038/s41375-023-01999-6
pmc: PMC10624608
doi:
Substances chimiques
Nucleophosmin
117896-08-9
Transcription Factors
0
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2187-2196Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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