Dawson, Amy and Zarou, Martha M. and Prasad, Bodhayan and Bittencourt-Silvestre, Joana and Zerbst, Désirée and Himonas, Ekaterini and Hsieh, Ya-Ching and van Loon, Isabel and Rodriguez Blanco, Giovanny and Ianniciello, Angela and Kerekes, Zsombor and Krishnan, Vaidehi and Agarwal, Puneet and Almasoudi, Hassan and McCluskey, Laura and Hopcroft, Lisa E.M. and Scott, Mary T. and Baquero, Pablo and Dunn, Karen and Vetrie, David and Copland, Mhairi and Bhatia, Ravi and Coffelt, Seth B. and Tiong, Ong Sin and Wheadon, Helen and Zanivan, Sara and Kirschner, Kristina and Helgason, G. Vignir (2024) Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nature Communications, 15: 1090. ISSN 2041-1723
AI Summary:
This study uses a chimeric mouse model to investigate the impact of chronic myeloid leukaemia (CML) on bone marrow macrophages. The results show that CML-exposed macrophages have reduced expression of CD36, which impairs their ability to clear apoptotic cells.AI Topics:
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.
Title | Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche |
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Creators | Dawson, Amy and Zarou, Martha M. and Prasad, Bodhayan and Bittencourt-Silvestre, Joana and Zerbst, Désirée and Himonas, Ekaterini and Hsieh, Ya-Ching and van Loon, Isabel and Rodriguez Blanco, Giovanny and Ianniciello, Angela and Kerekes, Zsombor and Krishnan, Vaidehi and Agarwal, Puneet and Almasoudi, Hassan and McCluskey, Laura and Hopcroft, Lisa E.M. and Scott, Mary T. and Baquero, Pablo and Dunn, Karen and Vetrie, David and Copland, Mhairi and Bhatia, Ravi and Coffelt, Seth B. and Tiong, Ong Sin and Wheadon, Helen and Zanivan, Sara and Kirschner, Kristina and Helgason, G. Vignir |
Identification Number | 10.1038/s41467-024-45471-0 |
Date | 5 February 2024 |
Divisions | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Publisher | Nature Research |
Additional Information | This work was supported by Friends of the Paul O’Gorman Leukaemia Research Centre (A.D., G.V.H., J.S., Z.K.), The Howat Foundation (G.V.H.), The Kay Kendall Leukaemia Fund (KKL698, P.B., G.V.H.), Tenovus Scotland (A.I., G.V.H.), Cancer Research UK (A29800 to S.Z. and A29754 to G.V.H.). |
URI | https://pub.demo35.eprints-hosting.org/id/eprint/364 |
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Item Type | Article |
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Depositing User | Unnamed user with email ejo1f20@soton.ac.uk |
Date Deposited | 11 Jun 2025 16:37 |
Revision | 37 |
Last Modified | 12 Jun 2025 10:16 |
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