Leukaemia Exposure Alters the Transcriptional Profile and Function of Macrophages in the Bone Marrow Niche

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.2704-2704
• Main Authors: Zarou, Martha M., Dawson, Amy, Prasad, Bodhayan, Bittencourt-Silvestre, Joana, Zerbst, Désirée, Rodriguez Blanco, Giovanny, Scott, Mary, Dunn, Karen, Krishnan, Vaidehi, Copland, Mhairi, Vetrie, David, Bhatia, Ravi, Coffelt, Seth, Ong, S.Tiong, Wheadon, Helen, Zanivan, Sara, Kirschner, Kristina, Helgason, G. Vignir
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-181630

These authors contributed equally to this work: Martha M. Zarou & Amy Dawson Macrophages are fundamental cells of the innate immune system. Bone marrow (BM) resident macrophages are involved in antigen presentation, phagocytosis, efferocytosis (clearing of apoptotic cells) and play a critical role in regulating haematopoietic stem cell (HSC) function. In chronic myeloid leukaemia (CML), the disease-initiating leukaemic stem cells (LSCs) modulate the BM microenvironment to support leukaemia maintenance and progression. However, whether the CML BM niche alters the function of macrophages remains unknown. Using single-cell RNA sequencing (scRNA-seq) of human BM mononuclear cells, we demonstrate heterogeneity of tissue resident macrophages, isolated from CML patients at diagnosis, which cluster separately from BM macrophages deriving from heathy individuals. As most BM macrophages at diagnosis express BCR::ABL1 and are sensitive to TKI treatment, we further investigated if Philadelphia chromosome negative (Ph -) macrophages play a major role in CML development. We applied a chimeric CML mouse model (SCLtTA/BCR::ABL1) and reveal that temporal depletion of macrophages prior to leukaemia induction (using CSF1R antagonist antibody), increases leukaemia burden and decreases survival of chimeric mice following BCR::ABL1 induction (p