AI Article Synopsis
- The study aims to identify specific gene/molecular fingerprints in endothelial cells related to multiple myeloma and understand how these cells contribute to the disease's progression from a less severe condition known as monoclonal gammopathy of undetermined significance.
- Researchers compared gene expression profiles of endothelial cells from both conditions using high-tech profiling methods and validated selected vascular markers through various biological techniques.
- The study found significant differences in gene expression that are linked to crucial cellular processes like growth and survival, revealing potential gene targets that could help categorize multiple myeloma more precisely and improve treatment strategies.
Article Abstract
Purpose: To determine a "gene/molecular fingerprint" of multiple myeloma endothelial cells and identify vascular mechanisms governing the malignant progression from quiescent monoclonal gammopathy of undetermined significance.
Experimental Design: Comparative gene expression profiling of multiple myeloma endothelial cells and monoclonal gammopathy of undetermined significance endothelial cells with the Affymetrix U133A Arrays was carried out in patients at diagnosis; expression and function of selective vascular markers was validated by real-time reverse transcriptase-PCR, Western blot, and small interfering RNA analyses.
Results: Twenty-two genes were found differentially expressed (14 down-regulated and eight up-regulated) at relatively high stringency in multiple myeloma endothelial cells compared with monoclonal gammopathy of undetermined significance endothelial cells. Functional annotation revealed a role of these genes in the regulation of extracellular matrix formation and bone remodeling, cell adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Validation was focused on six genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3, and SEPW1) not previously found to be functionally correlated to the overangiogenic phenotype of multiple myeloma endothelial cells in active disease. The small interfering RNA knockdown of BNIP3, IER3, and SEPW1 genes affected critical multiple myeloma endothelial cell functions correlated with the overangiogenic phenotype.
Conclusions: The distinct endothelial cell gene expression profiles and vascular phenotypes detected in this study may influence remodeling of the bone marrow microenvironment in patients with active multiple myeloma. A better understanding of the linkage between plasma cells and endothelial cells in multiple myeloma could contribute to the molecular classification of the disease and thus pinpoint selective gene targets for more effective antiangiogenic treatments.
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| http://dx.doi.org/10.1158/1078-0432.CCR-09-0040 | DOI Listing |
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