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Activated myeloid cell populations are increased in multiple myeloma (MM); however, the functional consequences of myeloid\u2010derived MPO within the myeloma microenvironment are unknown. Here, the role of MPO in MM pathogenesis was investigated, and the capacity for pharmacological inhibition of MPO to impede MM progression was evaluated. In the 5TGM1\u2010KaLwRij mouse model of myeloma, the early stages of tumour development were associated with an increase in CD11b<jats:sup>+<\/jats:sup> myeloid cell populations and an increase in <jats:italic>Mpo<\/jats:italic> expression within the bone marrow (BM). Interestingly, MM tumour cell homing was increased towards sites of elevated myeloid cell numbers and MPO activity within the BM. Mechanistically, MPO induced the expression of key MM growth factors, resulting in tumour cell proliferation and suppressed cytotoxic T\u2010cell activity. Notably, tumour growth studies in mice treated with a small\u2010molecule irreversible inhibitor of MPO (4\u2010ABAH) demonstrated a significant reduction in overall MM tumour burden. Taken together, our data demonstrate that MPO contributes to MM tumour growth, and that MPO\u2010specific inhibitors may provide a new therapeutic strategy to limit MM disease progression.<\/jats:p>","DOI":"10.1111\/bjh.19102","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T23:39:40Z","timestamp":1694561980000},"page":"614-624","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Myeloperoxidase creates a permissive microenvironmental niche for the progression of multiple myeloma"],"prefix":"10.1111","volume":"203","author":[{"given":"Connor M. 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