Abstract
Tissue inflammation is a hallmark of tumour microenvironments. In the bone marrow, tumour-associated inflammation impacts normal niches for haematopoietic progenitor cells and mature immune cells and supports the outgrowth and survival of malignant cells residing in these niche compartments. This Review provides an overview of our current understanding of inflammatory changes in the bone marrow microenvironment of myeloid and lymphoid malignancies, using acute myeloid leukaemia and multiple myeloma as examples and highlights unique and shared features of inflammation in niches for progenitor cells and plasma cells. Importantly, inflammation exerts profoundly different effects on normal bone marrow niches in these malignancies, and we provide context for possible drivers of these divergent effects. We explore the role of tumour cells in inflammatory changes, as well as the role of cellular constituents of normal bone marrow niches, including myeloid cells and stromal cells. Integrating knowledge of disease-specific dynamics of malignancy-associated bone marrow inflammation will provide a necessary framework for future targeting of these processes to improve patient outcome.
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Acknowledgements
T.C. is supported by a translational research award from the International Myeloma Society and Paula and Rodger Riney foundation. M.H.G.P.R. is supported by grants from the Dutch Cancer Society (KWF Kankerbestrijding, grant EMCRs 10488 and 11092).
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L.C. and M.H.G.P.R. researched data related to MDS and AML and contributed to the writing of sections related to these malignancies. M.M.E.D.J. and T.C. researched data for the article and wrote the manuscript. All authors reviewed and edited the manuscript before submission.
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Glossary
- AML1-ETO9a leukaemic mice
-
Model for human AML. Mouse HSCs are transduced with the AML1-ETO fusion oncoprotein, associated with translocation t(8;21) in patients225, and transplanted into lethally irradiated recipient mice that will rapidly develop a severe leukaemia resembling human AML226.
- MLL-AF9 leukaemic mice
-
Model for human AML. Mouse HSCs are transduced with the MLL-AF9 fusion oncoprotein, which mimics the t(9;11)(p22;q23) translocation found in human AML. Transfer of transduced cells in recipient mice induces AML227. MLL-AF9 knock-in mice were also generated, which spontaneously develop AML around 6 months of age228,229.
- MOPC-315.BM BALB/c myeloma mouse model
-
Model for human MM. Disease is established by intravenous injection of bone marrow-homing mouse myeloma cells (MOPC-315.BM) that were isolated and culture-adapted from a mineral oil-induced plasmacytoma in a BALB/c mouse230.
- NUP98-HOXD13 transgenic mice
-
Model for human MDS. Transgenic mice express a fusion oncoprotein of NUP98 and HOXD13, implicated in human MDS and AML. NUP98-HOXD13 transgenic mice develop features of human MDS, including cytopenias (bone marrow failure). Leukaemic transformation occurs in a subset of mice231.
- Vκ*MYC myeloma mouse model
-
Model for human MM. Spontaneous model driven by sporadic activation-induced cytidine deaminase (AID)-dependent MYC transgene expression in post-germinal centre B cells, leading to the development of MM in aged mice. Transplant of splenocytes of diseased Vκ*MYC mice to congenic mice can induce early-onset disease232.
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de Jong, M.M.E., Chen, L., Raaijmakers, M.H.G.P. et al. Bone marrow inflammation in haematological malignancies. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-01003-x
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DOI: https://doi.org/10.1038/s41577-024-01003-x
