Clonal dominance is an adverse prognostic factor in acute myeloid leukemia treated with intensive chemotherapy.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
19
11
2019
accepted:
16
06
2020
revised:
12
06
2020
pubmed:
26
6
2020
medline:
23
3
2021
entrez:
26
6
2020
Statut:
ppublish
Résumé
Intra-tumor heterogeneity portends poor outcome in many cancers. In AML, a higher number of drivers worsens prognosis. The Shannon Index is a robust metric of clonal heterogeneity that accounts for the number of clones, but also their relative abundance. We show that a Shannon Index can be estimated from bulk sequencing, which is correlated (ρ = 0.76) with clonal diversity from single-colony genotyping. In a discovery cohort of 292 patients with sequencing of 43 genes, a higher number of drivers (HR = 1.18, P = 0.028) and a lower Shannon Index (HR = 0.68, P = 0.048), the latter reflecting clonal dominance, are independently associated with worse OS independently of European LeukemiaNet 2017 risk. These findings are validated in an independent cohort of 1184 patients with 111-gene sequencing (number of drivers HR = 1.16, P = 1 × 10
Identifiants
pubmed: 32581253
doi: 10.1038/s41375-020-0932-8
pii: 10.1038/s41375-020-0932-8
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
712-723Références
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