Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 03 2023
08 03 2023
Historique:
received:
16
12
2021
accepted:
22
02
2023
entrez:
8
3
2023
pubmed:
9
3
2023
medline:
11
3
2023
Statut:
epublish
Résumé
Acute myeloid leukemia may be characterized by a fraction of leukemia stem cells (LSCs) that sustain disease propagation eventually leading to relapse. Yet, the contribution of LSCs to early therapy resistance and AML regeneration remains controversial. We prospectively identify LSCs in AML patients and xenografts by single-cell RNA sequencing coupled with functional validation by a microRNA-126 reporter enriching for LSCs. Through nucleophosmin 1 (NPM1) mutation calling or chromosomal monosomy detection in single-cell transcriptomes, we discriminate LSCs from regenerating hematopoiesis, and assess their longitudinal response to chemotherapy. Chemotherapy induced a generalized inflammatory and senescence-associated response. Moreover, we observe heterogeneity within progenitor AML cells, some of which proliferate and differentiate with expression of oxidative-phosphorylation (OxPhos) signatures, while others are OxPhos (low) miR-126 (high) and display enforced stemness and quiescence features. miR-126 (high) LSCs are enriched at diagnosis in chemotherapy-refractory AML and at relapse, and their transcriptional signature robustly stratifies patients for survival in large AML cohorts.
Identifiants
pubmed: 36890137
doi: 10.1038/s41467-023-36969-0
pii: 10.1038/s41467-023-36969-0
pmc: PMC9995364
doi:
Substances chimiques
MicroRNAs
0
MIRN126 microRNA, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1285Informations de copyright
© 2023. The Author(s).
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