Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes.
Multiple Myeloma
/ genetics
Humans
Chromatin Assembly and Disassembly
Tumor Microenvironment
/ genetics
Cell Line, Tumor
Mesenchymal Stem Cells
/ metabolism
Gene Expression Regulation, Neoplastic
Transcription, Genetic
Bone Marrow Cells
/ metabolism
Cell Movement
/ genetics
Stromal Cells
/ metabolism
Female
Male
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 May 2024
16 May 2024
Historique:
received:
06
01
2023
accepted:
12
04
2024
medline:
17
5
2024
pubmed:
17
5
2024
entrez:
16
5
2024
Statut:
epublish
Résumé
The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling. The expression of genes involved in these stromal interactions are observed in extramedullary disease in patients with myeloma and provides the rationale for survival of myeloma cells outside of the bone marrow microenvironment. Expression of these stromal interaction genes is also observed in a subset of patients with newly diagnosed myeloma and are akin to the transcriptional program of extramedullary disease. The presence of such adverse stromal interactions in newly diagnosed myeloma is associated with accelerated disease dissemination, predicts the early development of therapeutic resistance, and is of independent prognostic significance. These stromal cell induced transcriptomic and epigenomic changes both predict long-term outcomes and identify therapeutic targets in the tumor microenvironment for the development of novel therapeutic approaches.
Identifiants
pubmed: 38755155
doi: 10.1038/s41467-024-47793-5
pii: 10.1038/s41467-024-47793-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4139Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : P01-155258
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : 5P50 CA100707
Organisme : Department of Veterans Affairs | Office of Academic Affiliations, Department of Veterans Affairs (OAA, VA)
ID : I01BX001584-01
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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