A longitudinal single-cell atlas of treatment response in pediatric AML.
acute myeloid leukemia
hematopoiesis
heterogeneity
leukemia
pediatric cancer
single-cell ATAC-seq
single-cell RNA-seq
therapy resistance
transcriptional regulation
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
11 Dec 2023
11 Dec 2023
Historique:
received:
17
04
2023
revised:
15
09
2023
accepted:
26
10
2023
pubmed:
18
11
2023
medline:
18
11
2023
entrez:
17
11
2023
Statut:
ppublish
Résumé
Pediatric acute myeloid leukemia (pAML) is characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains understudied in pediatric patients. We used single-cell RNA sequencing and single-cell ATAC sequencing to profile 28 patients representing different pAML subtypes at diagnosis, remission and relapse. At diagnosis, cellular composition differed between genetic subgroups. Upon relapse, cellular hierarchies transitioned toward a more primitive state regardless of subtype. Primitive cells in the relapsed tumor were distinct compared to cells at diagnosis, with under-representation of myeloid transcriptional programs and over-representation of other lineage programs. In some patients, this was accompanied by the appearance of a B-lymphoid-like hierarchy. Our data thus reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potentially targetable processes.
Identifiants
pubmed: 37977148
pii: S1535-6108(23)00364-1
doi: 10.1016/j.ccell.2023.10.008
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2117-2135.e12Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.