title: Serum concentrations of DKK-1 decrease in patients with multiple myeloma responding to anti-myeloma treatment.
abstract: Lytic bone destruction is a hallmark of multiple myeloma (MM) and is because of an uncoupling of bone remodeling. Secretion of Dickkopf (DKK)-1 by myeloma cells is a major factor which causes inhibition of osteoblast precursors. In this study, the effect of different treatment regimens for MM on serum DKK-1 was evaluated and correlated with the response to treatment in 101 myeloma patients receiving bortezomib, thalidomide, lenalidomide, adriamycin and dexamethasone (AD) or high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT). At baseline, myeloma patients had increased serum DKK-1 as compared with patients with MGUS (mean 3786 pg/mL vs. 1993 pg/mL). There was no difference between previously untreated MM patients and patients at relapse. A significant decrease of DKK-1 after therapy was seen in the following groups: Bortezomib (4059 pg/mL vs. 1862 pg/mL, P = 0.016), lenalidomide (11837 pg/mL vs. 4374 pg/mL, P = 0.039), AD (1668 pg/mL vs. 1241 pg/mL, P = 0.016), and AD + HDCT + ASCT (2446 pg/mL vs. 1082 pg/mL, P = 0.001). Thalidomide led to a non-significant decrease in DKK-1 (1705 pg/mL vs. 1269 pg/mL, P = 0.081). Within all groups, a significant decrease of DKK-1 was only seen in responders (i.e. patients achieving complete remission or partial remission), but not in non-responders. We show for the first time that serum DKK-1 levels decrease in myeloma patients responding to treatment, irrespective of the regimen chosen. These data suggest that myeloma cells are the main source of circulating DKK-1 protein and provide a framework for clinical trials on anti-DKK-1 treatment in MM.
authors.affiliation: Department of Hematology and Oncology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heider
authors.forename: Martin
authors.initials: M
authors.lastname: Kaiser
authors.forename: Maren
authors.initials: M
authors.lastname: Mieth
authors.forename: Britta
authors.initials: B
authors.lastname: Lamottke
authors.forename: Jessica
authors.initials: J
authors.lastname: Rademacher
authors.forename: Christian
authors.initials: C
authors.lastname: Jakob
authors.forename: Edgar
authors.initials: E
authors.lastname: Braendle
authors.forename: David
authors.initials: D
authors.lastname: Stover
authors.forename: Orhan
authors.initials: O
authors.lastname: Sezer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy*; D016879:Salvage Therapy
chemical_list: D000970:Antineoplastic Agents; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins