Williams, C.M.D.Noll, J.E.Bradey, A.L.Duggan, J.Wilczek, V.J.Masavuli, M.G.Grubor‐Bauk, B.Panagopoulos, R.A.Hewett, D.R.Mrozik, K.M.Zannettino, A.C.W.Vandyke, K.Panagopoulos, V.2023-09-182023-09-182023British Journal of Haematology, 2023; 203(4):614-6240007-10481365-2141https://hdl.handle.net/2440/139495First published: 12 September 2023Expression of myeloperoxidase (MPO), a key inflammatory enzyme restricted to myeloid cells, is negatively associated with the development of solid tumours. Activated myeloid cell populations are increased in multiple myeloma (MM); however, the functional consequences of myeloid-derived 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-KaLwRij mouse model of myeloma, the early stages of tumour development were associated with an increase in CD11b+ myeloid cell populations and an increase in Mpo 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-cell activity. Notably, tumour growth studies in mice treated with a small-molecule irreversible inhibitor of MPO (4-ABAH) demonstrated a significant reduction in overall MM tumour burden. Taken together, our data demonstrate that MPO contributes to MM tumour growth, and that MPO-specific inhibitors may provide a new therapeutic strategy to limit MM disease progression.en© 2023 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.immune suppression; multiple myeloma; myeloid-derived suppressor cells; myeloperoxidaseJournal article10.1111/bjh.191022023-09-18655972Williams, C.M.D. [0000-0003-4034-8557]Noll, J.E. [0000-0001-7375-635X]Masavuli, M.G. [0000-0001-7287-6595]Mrozik, K.M. [0000-0002-4890-8208]Zannettino, A.C.W. [0000-0002-6646-6167]Vandyke, K. [0000-0002-1033-849X]Panagopoulos, V. [0000-0002-6879-1262]