Identification of cells of leukemic stem cell origin with non-canonical regenerative properties.

Regen71 acute myeloid leukemia chemotherapy injury leukemia stem cells non-canonical regeneration regeneration enriched cells relapse

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
23 Mar 2024
Historique:
received: 19 05 2023
revised: 19 10 2023
accepted: 04 03 2024
medline: 7 4 2024
pubmed: 7 4 2024
entrez: 6 4 2024
Statut: aheadofprint

Résumé

Despite most acute myeloid leukemia (AML) patients entering remission following chemotherapy, outcomes remain poor due to surviving leukemic cells that contribute to relapse. The nature of these enduring cells is poorly understood. Here, through temporal single-cell transcriptomic characterization of AML hierarchical regeneration in response to chemotherapy, we reveal a cell population: AML regeneration enriched cells (RECs). RECs are defined by CD74/CD68 expression, and although derived from leukemic stem cells (LSCs), are devoid of stem/progenitor capacity. Based on REC in situ proximity to CD34-expressing cells identified using spatial transcriptomics on AML patient bone marrow samples, RECs demonstrate the ability to augment or reduce leukemic regeneration in vivo based on transfusion or depletion, respectively. Furthermore, RECs are prognostic for patient survival as well as predictive of treatment failure in AML cohorts. Our study reveals RECs as a previously unknown functional catalyst of LSC-driven regeneration contributing to the non-canonical framework of AML regeneration.

Identifiants

DOI: 10.1016/j.xcrm.2024.101485 PMID: 38582086
pubmed: 38582086
pii: S2666-3791(24)00131-9
doi: 10.1016/j.xcrm.2024.101485
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101485

Informations de copyright

Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Cameron G Hollands (CG)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Allison L Boyd (AL)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Xueli Zhao (X)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Jennifer C Reid (JC)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Charisa Henly (C)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Amro ElRafie (A)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

David Boylan (D)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Emily Broder (E)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Olivia Kalau (O)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Paige Johnson (P)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Alyssa Mark (A)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Jamie McNicol (J)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

Anargyros Xenocostas (A)

Department of Medicine, Division of Hematology, Schulich School of Medicine, University of Western Ontario, London, Ontario N6A 3K7, Canada; Hematology Exploration and Applications in Leukemia (HEAL) Program, Hamilton, ON, Canada.

Tobias Berg (T)

Hematology Exploration and Applications in Leukemia (HEAL) Program, Hamilton, ON, Canada; Department of Oncology, McMaster University, Hamilton, ON L8S 4L8, Canada.

Ronan Foley (R)

Hematology Exploration and Applications in Leukemia (HEAL) Program, Hamilton, ON, Canada; Department of Oncology, McMaster University, Hamilton, ON L8S 4L8, Canada.

Michael Trus (M)

Hematology Exploration and Applications in Leukemia (HEAL) Program, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.

Brian Leber (B)

Hematology Exploration and Applications in Leukemia (HEAL) Program, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.

Alejandro Garcia-Horton (A)

Hematology Exploration and Applications in Leukemia (HEAL) Program, Hamilton, ON, Canada; Department of Oncology, McMaster University, Hamilton, ON L8S 4L8, Canada.

Clinton Campbell (C)

Hematology Exploration and Applications in Leukemia (HEAL) Program, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.

Mickie Bhatia (M)

Michael G. DeGroote School of Medicine, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada; Hematology Exploration and Applications in Leukemia (HEAL) Program, Hamilton, ON, Canada. Electronic address: mbhatia@mcmaster.ca.

Classifications MeSH