Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 Feb 2024
05 Feb 2024
Historique:
received:
29
04
2022
accepted:
25
01
2024
medline:
7
2
2024
pubmed:
6
2
2024
entrez:
5
2
2024
Statut:
epublish
Résumé
Macrophages are fundamental cells of the innate immune system that support normal haematopoiesis and play roles in both anti-cancer immunity and tumour progression. Here we use a chimeric mouse model of chronic myeloid leukaemia (CML) and human bone marrow (BM) derived macrophages to study the impact of the dysregulated BM microenvironment on bystander macrophages. Utilising single-cell RNA sequencing (scRNA-seq) of Philadelphia chromosome (Ph) negative macrophages we reveal unique subpopulations of immature macrophages residing in the CML BM microenvironment. CML exposed macrophages separate from their normal counterparts by reduced expression of the surface marker CD36, which significantly reduces clearance of apoptotic cells. We uncover aberrant production of CML-secreted factors, including the immune modulatory protein lactotransferrin (LTF), that suppresses efferocytosis, phagocytosis, and CD36 surface expression in BM macrophages, indicating that the elevated secretion of LTF is, at least partially responsible for the supressed clearance function of Ph- macrophages.
Identifiants
pubmed: 38316788
doi: 10.1038/s41467-024-45471-0
pii: 10.1038/s41467-024-45471-0
pmc: PMC10844594
doi:
Substances chimiques
Fusion Proteins, bcr-abl
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1090Subventions
Organisme : Cancer Research UK
ID : 29754
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 29800
Pays : United Kingdom
Informations de copyright
© 2024. The Author(s).
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