Serum concentrations of DKK-1 decrease in patients with multiple myeloma responding to anti-myeloma treatment
Serum concentrations of DKK-1 decrease in patients with multiple myeloma responding to anti-myeloma treatment
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DOI：
10.1111/j.1600-0609.2008.01164.x
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发表时间：
2009-01-01
影响因子：
3.1
通讯作者：
Sezer, Orhan
中科院分区：
文献类型：
--
作者：
Heider, Ulrike;Kaiser, Martin;Sezer, Orhan
溶骨性破坏是多发性骨髓瘤（MM）的一个特征，是由于骨重塑失衡所致。骨髓瘤细胞分泌的Dickkopf -1（DKK -1）是导致成骨细胞前体受抑制的一个主要因素。在这项研究中，评估了MM的不同治疗方案对血清DKK -1的影响，并将其与101例接受硼替佐米、沙利度胺、来那度胺、阿霉素和地塞米松（AD）或大剂量化疗（HDCT）后行自体干细胞移植（ASCT）的骨髓瘤患者的治疗反应相关联。在基线水平时，与意义未明的单克隆丙种球蛋白病（MGUS）患者相比，骨髓瘤患者的血清DKK -1升高（平均3786 pg/mL对1993 pg/mL）。初治的MM患者和复发患者之间无差异。在以下几组中，治疗后DKK -1显著下降：硼替佐米组（4059 pg/mL对1862 pg/mL，P = 0.016），来那度胺组（11837 pg/mL对4374 pg/mL，P = 0.039），AD组（1668 pg/mL对1241 pg/mL，P = 0.016），以及AD + HDCT + ASCT组（2446 pg/mL对1082 pg/mL，P = 0.001）。沙利度胺导致DKK -1下降不显著（1705 pg/mL对1269 pg/mL，P = 0.081）。在所有组中，DKK -1显著下降仅见于有反应者（即达到完全缓解或部分缓解的患者），而非无反应者。我们首次表明，无论选择何种方案，对治疗有反应的骨髓瘤患者血清DKK -1水平均下降。这些数据表明骨髓瘤细胞是循环中DKK -1蛋白的主要来源，并为MM中抗DKK -1治疗的临床试验提供了框架。
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.