title: The cytokine/chemokine pattern in the bone marrow environment of multiple myeloma patients.
abstract: OBJECTIVE
  The interaction of multiple myeloma (MM) with its bone marrow (BM) microenvironment is important for the homing pattern, survival, and proliferation of malignant plasma cells. We aimed at answering the question which cytokines, chemokines, and growth factors are typically found in the BM of untreated MM patients as well as in MM patients after allogeneic stem cell transplantation (alloSCT).
  
  
  METHODS
  We determined the concentrations of 34 cytokines/chemokines in the supernatants of 10 myeloma cell lines, as well as in the plasma derived from BM and peripheral blood samples of 10 newly diagnosed MM patients, 20 MM patients who had received allogeneic stem cell transplantation (alloSCT), and 20 healthy donors.
  
  
  RESULTS
  Besides cytokines/chemokines known to be secreted by myeloma cell lines, such as interleukin-1 receptor antagonist (IL-1RA), IL-8, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, and MIP-3α, we also detected significant levels of epidermal growth factor (EGF), hepatocyte growth factor (HGF), IL2R, IL-12p40/p70, IL-22, interferon-γ (IFN-γ)-inducible protein 10 (IP-10), monokine induced by IFN-γ (MIG), and regulated on activation normally T-cell expressed and secreted (RANTES) in culture supernatants. The BM environment in MM patients evidenced elevated concentrations of HGF, IL-2R, IL-16, EGF, IL-1RA, IP-10, MCP-1, and monokine induced by IFN-γ. Additionally, in the BM of MM patients post alloSCT, we found selectively elevated concentration of IL-4, IL-6, IL-8, IL-12p40/p70, and eotaxin. Eotaxin levels were particularly high in patients with chronic graft-vs-host disease.
  
  
  CONCLUSIONS
  Our study demonstrates characteristic cytokine/chemokine patterns in the BM environment of MM patients before and after alloSCT. Certain factors, such as MIP-1α, MCP-1, HGF, IL-16, IP-10, and eotaxin, might not only be developed into diagnostic instruments and/or predictive biomarkers, but are also potential targets for future myeloma- or graft-vs-host disease-specific therapies.
authors.affiliation: Department of Internal Medicine II (Oncology/Hematology/Stem Cell Transplantation), University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. y.cao@uke.uni-hamburg.de
authors.forename: Yanran
authors.initials: Y
authors.lastname: Cao
authors.forename: Tim
authors.initials: T
authors.lastname: Luetkens
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kobold
authors.forename: York
authors.initials: Y
authors.lastname: Hildebrandt
authors.forename: Maja
authors.initials: M
authors.lastname: Gordic
authors.forename: Nesrine
authors.initials: N
authors.lastname: Lajmi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Meyer
authors.forename: Katrin
authors.initials: K
authors.lastname: Bartels
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
mesh_terms: D001853:Bone Marrow / Q000378:metabolism*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000097:blood* / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines