Cutaneous metastatic plasmacytomas with tropism for a previously injured limb

Pereira, Marta Almeida; Baudrier, Teresa; Costa, Alice Paes Rozado; Magalhães, João Pompeu Frota; Azevedo, Filomena

doi:10.5070/d337n527v0

Cited by 6 publications

(5 citation statements)

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“…Furthermore, we show an indirect effect on 5TGM1 MM PC proliferation when cultured with CM from MPO‐treated OP9 cells, which may be attributable to the upregulation of IL6. Interestingly, several case studies have detailed plasmacytoma occurrence at sites of local trauma and inflammation in MGUS patients, 47 , 48 , 49 supporting the hypothesis that inflammation represents a key driving factor in the homing and/or outgrowth of malignant PCs. Collectively, these studies suggest that local trauma and the associated induction of pro‐inflammatory pathways, which we postulate include increased MPO activity, aid in establishing a favourable niche for MM development.…”

Section: Discussionmentioning

confidence: 91%

Myeloperoxidase creates a permissive microenvironmental niche for the progression of multiple myeloma

Williams,

Noll,

Bradey

et al. 2023

Br J Haematol

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SummaryExpression 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.

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Section: Discussionmentioning

confidence: 91%

Myeloperoxidase creates a permissive microenvironmental niche for the progression of multiple myeloma

Williams,

Noll,

Bradey

et al. 2023

Br J Haematol

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“…3 As such, skin findings are often associated with higher tumor burden and more aggressive disease. 4 Cutaneous plasmacytomas may occur secondary to multiple myeloma or as primary lesions, without evidence of an underlying plasma cell dyscrasia. All classes of immunoglobulins have been implicated in cases of secondary plasmacytomas, although subtype IgG is the most common.…”

Section: Discussionmentioning

confidence: 99%

“…8 Unfortunately, the presence of extramedullary involvement at any time during the disease course has been associated with poor prognosis regardless of therapy. 1,4 Currently, various options exist for the treatment of multiple myeloma including immunomodulatory agents, proteasome inhibitors, cytotoxic agents, and stem cell transplantation. 9 In relapsed or refractory disease, salvage options have included DCEP, which has shown a beneficial response but is associated with significant treatmentrelated mortality.…”

Section: Discussionmentioning

confidence: 99%

“…Some suggest a correlation between the proliferation of plasma cells outside the bone marrow and total body tumor cell mass . As such, skin findings are often associated with higher tumor burden and more aggressive disease . Cutaneous plasmacytomas may occur secondary to multiple myeloma or as primary lesions, without evidence of an underlying plasma cell dyscrasia.…”

Section: Discussionmentioning

confidence: 99%

“…While multiple myeloma is considered an incurable disease, studies in the last decade report an increase in 5-year survival rates from 28% to 49%; which has been largely attributed to novel therapies including immunomodulatory agents and proteasome inhibitors . Unfortunately, the presence of extramedullary involvement at any time during the disease course has been associated with poor prognosis regardless of therapy . Currently, various options exist for the treatment of multiple myeloma including immunomodulatory agents, proteasome inhibitors, cytotoxic agents, and stem cell transplantation .…”

Section: Discussionmentioning

confidence: 99%

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