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An atlas of the bone marrow bone proteome in patients with dysproteinemias

Multiple myeloma (MM) bone disease is a significant cause of morbidity but there is a paucity of data on the impact of malignant plasma cells on adjacent trabecular bone within the BM. Here, we characterize the proteome of trabecular bone tissue from BM biopsies of 56 patients with monoclonal gammop...

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Autores principales: Ho, Matthew, Dasari, Surendra, Visram, Alissa, Drake, Matthew, Charlesworth, Cristine, Johnson, Kenneth, Pujari, Ganesh, Jevremovic, Dragan, Kourelis, Taxiarchis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900982/
https://www.ncbi.nlm.nih.gov/pubmed/36747663
http://dx.doi.org/10.21203/rs.3.rs-2468383/v1
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author Ho, Matthew
Dasari, Surendra
Visram, Alissa
Drake, Matthew
Charlesworth, Cristine
Johnson, Kenneth
Pujari, Ganesh
Jevremovic, Dragan
Kourelis, Taxiarchis
author_facet Ho, Matthew
Dasari, Surendra
Visram, Alissa
Drake, Matthew
Charlesworth, Cristine
Johnson, Kenneth
Pujari, Ganesh
Jevremovic, Dragan
Kourelis, Taxiarchis
author_sort Ho, Matthew
collection PubMed
description Multiple myeloma (MM) bone disease is a significant cause of morbidity but there is a paucity of data on the impact of malignant plasma cells on adjacent trabecular bone within the BM. Here, we characterize the proteome of trabecular bone tissue from BM biopsies of 56 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM), newly diagnosed (NDMM), relapsed MM (RMM), and normal controls. Proteins involved in extracellular matrix (ECM) formation and immunity pathways were decreased in SMM and active MM. Among the proteins most decreased were immunoglobulins, type IV collagen, and TIMP3, suggesting increased immunoparesis and decreased ECM remodelling within trabecular bone. Proteins most increased in SMM/MM were APP (enhances osteoclast activity), ENPP1 (enhances bone mineralization), and MZB1 (required for normal plasmablast differentiation). Pathway analyses showed that proteins involved in gamma -carboxylation, a pathway implicated in osteocalcin function, osteoblast differentiation, and normal hematopoiesis, were also overexpressed in SMM/MM. This study is the first comprehensive proteomic atlas of the BM bone proteome in dysproteinemias. We identify new key proteins and pathways for MM bone disease and potentially impaired hematopoiesis, and show for the first time that gamma -carboxylation pathways are increased in the bone tissue of SMM/MM.
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spelling pubmed-99009822023-02-07 An atlas of the bone marrow bone proteome in patients with dysproteinemias Ho, Matthew Dasari, Surendra Visram, Alissa Drake, Matthew Charlesworth, Cristine Johnson, Kenneth Pujari, Ganesh Jevremovic, Dragan Kourelis, Taxiarchis Res Sq Article Multiple myeloma (MM) bone disease is a significant cause of morbidity but there is a paucity of data on the impact of malignant plasma cells on adjacent trabecular bone within the BM. Here, we characterize the proteome of trabecular bone tissue from BM biopsies of 56 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM), newly diagnosed (NDMM), relapsed MM (RMM), and normal controls. Proteins involved in extracellular matrix (ECM) formation and immunity pathways were decreased in SMM and active MM. Among the proteins most decreased were immunoglobulins, type IV collagen, and TIMP3, suggesting increased immunoparesis and decreased ECM remodelling within trabecular bone. Proteins most increased in SMM/MM were APP (enhances osteoclast activity), ENPP1 (enhances bone mineralization), and MZB1 (required for normal plasmablast differentiation). Pathway analyses showed that proteins involved in gamma -carboxylation, a pathway implicated in osteocalcin function, osteoblast differentiation, and normal hematopoiesis, were also overexpressed in SMM/MM. This study is the first comprehensive proteomic atlas of the BM bone proteome in dysproteinemias. We identify new key proteins and pathways for MM bone disease and potentially impaired hematopoiesis, and show for the first time that gamma -carboxylation pathways are increased in the bone tissue of SMM/MM. American Journal Experts 2023-01-23 /pmc/articles/PMC9900982/ /pubmed/36747663 http://dx.doi.org/10.21203/rs.3.rs-2468383/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Article
Ho, Matthew
Dasari, Surendra
Visram, Alissa
Drake, Matthew
Charlesworth, Cristine
Johnson, Kenneth
Pujari, Ganesh
Jevremovic, Dragan
Kourelis, Taxiarchis
An atlas of the bone marrow bone proteome in patients with dysproteinemias
title An atlas of the bone marrow bone proteome in patients with dysproteinemias
title_full An atlas of the bone marrow bone proteome in patients with dysproteinemias
title_fullStr An atlas of the bone marrow bone proteome in patients with dysproteinemias
title_full_unstemmed An atlas of the bone marrow bone proteome in patients with dysproteinemias
title_short An atlas of the bone marrow bone proteome in patients with dysproteinemias
title_sort atlas of the bone marrow bone proteome in patients with dysproteinemias
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900982/
https://www.ncbi.nlm.nih.gov/pubmed/36747663
http://dx.doi.org/10.21203/rs.3.rs-2468383/v1
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