title: Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ria
authors.forename: Katia
authors.initials: K
authors.lastname: Todoerti
authors.forename: Simona
authors.initials: S
authors.lastname: Berardi
authors.forename: Addolorata Maria Luce
authors.initials: AM
authors.lastname: Coluccia
authors.forename: Annunziata
authors.initials: A
authors.lastname: De Luisi
authors.forename: Michela
authors.initials: M
authors.lastname: Mattioli
authors.forename: Domenica
authors.initials: D
authors.lastname: Ronchetti
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Attilio
authors.initials: A
authors.lastname: Guarini
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051151:Selenoprotein W / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C090121:BNIP3 protein, human; C099815:IER3 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C495240:SELENOW protein, human; D051151:Selenoprotein W