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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Serum concentrations of DKK-1 decrease in patients with multiple myeloma responding to anti-myeloma treatment
Ulrike Heider1, Martin Kaiser, Maren Mieth
1Department of Hematology and Oncology, Charité - Universitaetsmedizin Berlin, Berlin, Germany.
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.
Insights
Serum Dickkopf-1 (DKK-1) levels are elevated in multiple myeloma (MM) patients. Treatment response in MM correlates with a significant decrease in DKK-1, suggesting it
Area of Science:
- Oncology
- Bone Biology
- Medical Biochemistry
Background:
- Multiple myeloma (MM) is characterized by lytic bone destruction due to dysregulated bone remodeling.
- Myeloma cells secrete Dickkopf-1 (DKK-1), a protein that inhibits osteoblast precursor differentiation.
- Elevated serum DKK-1 levels are observed in MM patients compared to those with monoclonal gammopathy of undetermined significance (MGUS).
Purpose of the Study:
- To investigate the impact of various multiple myeloma treatment regimens on serum DKK-1 levels.
- To correlate changes in serum DKK-1 with treatment response in MM patients.
- To explore the potential of DKK-1 as a biomarker for MM treatment efficacy.
Main Methods:
- Serum DKK-1 levels were measured at baseline and post-therapy in 101 MM patients.
- Patients received treatments including bortezomib, thalidomide, lenalidomide, adriamycin and dexamethasone (AD), or high-dose chemotherapy with autologous stem cell transplantation (HDCT + ASCT).
- DKK-1 levels were analyzed in relation to treatment regimens and patient response (complete or partial remission).
Main Results:
- MM patients exhibited significantly higher baseline serum DKK-1 than MGUS patients.
- Significant decreases in serum DKK-1 were observed following treatment with bortezomib, lenalidomide, AD, and AD + HDCT + ASCT.
- A significant reduction in DKK-1 was exclusively observed in patients achieving remission, irrespective of the treatment regimen.
Conclusions:
- Serum DKK-1 levels decrease in multiple myeloma patients who respond to therapy.
- Myeloma cells are identified as the primary source of circulating DKK-1.
- These findings support DKK-1 as a potential biomarker for treatment response and suggest anti-DKK-1 therapies for MM.
