Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche

Amy Dawson, Martha M. Zarou, Bodhayan Prasad, Joana Bittencourt-Silvestre, Désirée Zerbst, Ekaterini Himonas, Ya-Ching Hsieh, Isabel Loon, Giovanny Rodriguez Blanco, Angela Ianniciello, Zsombor Kerekes, Vaidehi Krishnan, Puneet Agarwal, Hassan Almasoudi, Laura McCluskey, Lisa E. M. Hopcroft, Mary T. Scott, Pablo Baquero, Karen Dunn, David Vetrie, Mhairi Copland, Ravi Bhatia, Seth B. Coffelt, Ong Sin Tiong, Helen Wheadon, Sara Zanivan, Kristina Kirschner () and G. Vignir Helgason ()
Additional contact information
Amy Dawson: University of Glasgow
Martha M. Zarou: University of Glasgow
Bodhayan Prasad: University of Glasgow
Joana Bittencourt-Silvestre: University of Glasgow
Désirée Zerbst: University of Glasgow
Ekaterini Himonas: University of Glasgow
Ya-Ching Hsieh: Cancer Research UK Scotland Institute
Isabel Loon: University of Glasgow
Giovanny Rodriguez Blanco: Cancer Research UK Scotland Institute
Angela Ianniciello: University of Glasgow
Zsombor Kerekes: University of Glasgow
Vaidehi Krishnan: Cancer & Stem Cell Biology Signature Research Programme, Duke-NUS Medical School
Puneet Agarwal: University of Alabama at Birmingham
Hassan Almasoudi: University of Glasgow
Laura McCluskey: University of Glasgow
Lisa E. M. Hopcroft: University of Glasgow
Mary T. Scott: University of Glasgow
Pablo Baquero: University of Glasgow
Karen Dunn: University of Glasgow
David Vetrie: University of Glasgow
Mhairi Copland: University of Glasgow
Ravi Bhatia: University of Alabama at Birmingham
Seth B. Coffelt: University of Glasgow
Ong Sin Tiong: Cancer & Stem Cell Biology Signature Research Programme, Duke-NUS Medical School
Helen Wheadon: University of Glasgow
Sara Zanivan: University of Glasgow
Kristina Kirschner: University of Glasgow
G. Vignir Helgason: University of Glasgow

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-45471-0

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