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

Author

Listed:
  • 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
    Najran University)

  • Laura McCluskey

    (University of Glasgow)

  • Lisa E. M. Hopcroft

    (University of Glasgow)

  • Mary T. Scott

    (University of Glasgow)

  • Pablo Baquero

    (University of Glasgow
    Universidad de Alcalá, Facultad de Medicina y Ciencias de la Salud, Dpto. de Biología de Sistemas, Unidad de Bioquímica y Biología Molecular)

  • 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
    Cancer Research UK Scotland Institute)

  • Ong Sin Tiong

    (Cancer & Stem Cell Biology Signature Research Programme, Duke-NUS Medical School)

  • Helen Wheadon

    (University of Glasgow)

  • Sara Zanivan

    (University of Glasgow
    Cancer Research UK Scotland Institute)

  • Kristina Kirschner

    (University of Glasgow
    Cancer Research UK Scotland Institute)

  • G. Vignir Helgason

    (University of Glasgow)

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.

Suggested Citation

  • Amy Dawson & Martha M. Zarou & Bodhayan Prasad & Joana Bittencourt-Silvestre & Désirée Zerbst & Ekaterini Himonas & Ya-Ching Hsieh & Isabel Loon & Giovanny Rodriguez Blanco & Angela Ianniciello & Zsom, 2024. "Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45471-0
    DOI: 10.1038/s41467-024-45471-0
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    References listed on IDEAS

    as
    1. Phillip M. Brailey & Lauren Evans & Juan Carlos López-Rodríguez & Anthony Sinadinos & Victoria Tyrrel & Gavin Kelly & Valerie O’Donnell & Peter Ghazal & Susan John & Patricia Barral, 2022. "CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Juan R. Hernandez-Fernaud & Elena Ruengeler & Andrea Casazza & Lisa J. Neilson & Ellie Pulleine & Alice Santi & Shehab Ismail & Sergio Lilla & Sandeep Dhayade & Iain R. MacPherson & Iain McNeish & Dar, 2017. "Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity," Nature Communications, Nature, vol. 8(1), pages 1-17, April.
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