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Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes
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Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes
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Journal Article
Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes
2024
Overview
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.
Bone marrow stromal cells (BMSCs) are known to promote the development of drug resistance. Here, the authors investigate the chromatin remodeling and associated changes in gene expression in the multiple myeloma (MM) cells following their interactions with BMSCs, which are also observed in extramedullary disease (EMD).
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/61
/ 38/91
/ Bone Marrow Cells - metabolism
/ Chromatin Assembly and Disassembly
/ Female
/ Gene Expression Regulation, Neoplastic
/ Genes
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mesenchymal Stem Cells - metabolism
/ Mesenchymal Stem Cells - pathology
/ Multiple Myeloma - metabolism
/ Multiple Myeloma - pathology
/ Science
/ Survival
