title: Angiogenic cytokines profile in smoldering multiple myeloma: no difference compared to MGUS but altered compared to symptomatic myeloma.
abstract: BACKGROUND
  Symptomatic multiple myeloma (MM) evolves from an asymptomatic precursor state termed monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM). Angiogenesis plays a key role in the pathogenesis of MM but there are very limited data for angiogenesis in SMM.
  
  
  METHODS
  We measured the circulating levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and angiogenin in 54 patients with SMM. The results were compared with those of 27 MGUS patients, 55 MM patients, and 22 healthy controls. The expression of VEGF-A gene was also evaluated in 10 patients with SMM, 10 with symptomatic MM, and 10 with MGUS.
  
  
  RESULTS
  The ratio of circulating Ang-1/Ang-2 was reduced in MM patients with symptomatic disease due to a dramatic increase of Ang-2 (p<0.001), but not in patients with SMM or MGUS, in whom it did not differ compared to controls. VEGF and angiogenin were increased in all patients compared to controls. However, circulating VEGF was higher in symptomatic MM compared to SMM and MGUS, while angiogenin was reduced. There were no differences in the expression of VEGF-A among the 3 patients categories.
  
  
  CONCLUSIONS
  SMM has a circulating angiogenic cytokine profile similar to that of MGUS, but has altered profile compared to symptomatic MM. Thus, in the progression of MGUS to SMM, circulating angiogenic cytokines seem to be the same. On the contrary, in symptomatic myeloma, the alterations of angiopoietins along with VEGF contribute to myeloma cell growth, supporting the target of these molecules for the development of novel anti-myeloma agents.
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gkotzamanidou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, "Laiko" General Hospital, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Christoulas
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
authors.forename: Vasillis L
authors.initials: VL
authors.lastname: Souliotis
authors.affiliation: Department of Medical Research, 251 General Air Force Hospital, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papatheodorou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000097:blood*; D009101:Multiple Myeloma / Q000097:blood* / Q000145:classification / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000097:blood; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; C046366:angiogenin; D012259:Ribonuclease, Pancreatic