Jakob Christian, Goerke Andrea, Terpos Evangelos, Sterz Jan, Heider Ulrike, Kühnhardt Dagmar, Ziefle Susanne, Kleeberg Lorenz, Mieth Maren, Metzler Ivana von, Müller Christian, Sezer Orhan
Department of Hematology and Oncology, Charité, Universitätsmedizin Berlin, Berlin 10117, Germany.
Clin Lymphoma Myeloma. 2009 Dec;9(6):430-5. doi: 10.3816/CLM.2009.n.085.
Receptor activator of nuclear factor-kappaB ligand (RANKL) plays a key role in osteoclast activation in myeloma bone disease. The increased expression of RANKL in the bone marrow microenvironment was demonstrated in several studies, but there are only rare data on circulating RANKL levels in patients with multiple myeloma (MM).
In the current study, we investigated the clinical significance of serum RANKL levels, using an enzyme-linked immunosorbent assay test that detects both free and osteoprotegerin (OPG)-bound RANKL (total-RANKL, tRANKL) in patients with newly diagnosed MM (n = 93) and monoclonal gammopathy of undetermined significance (MGUS; n = 20) compared with healthy controls (n = 20).
Circulating serum tRANKL was significantly elevated in patients with MM compared with controls (P < .001) or MGUS (P < .001). Furthermore, tRANKL levels were higher in smoldering MM versus MGUS (P = .031) and in symptomatic versus smoldering MM (P < .001). Serum tRANKL increased parallel to International Staging System stages I to III (P = .004) and correlated with the presence of lytic bone lesions (P < .001). Total-RANKL was a prognostic factor for overall survival in symptomatic MM (P = .043). A significantly longer progression-free survival was observed in patients with a > 50% decrease in tRANKL levels after 3 months of combined chemotherapy and bisphosphonate treatment.
Our study demonstrates for the first time that serum tRANKL reflects advanced disease, lytic bone destruction, and poor prognosis in MM.
核因子κB受体活化因子配体（RANKL）在骨髓瘤骨病的破骨细胞活化中起关键作用。多项研究证实骨髓微环境中RANKL表达增加，但关于多发性骨髓瘤（MM）患者循环RANKL水平的数据却很少。
在本研究中，我们采用酶联免疫吸附测定法检测新诊断MM患者（n = 93）、意义未明的单克隆丙种球蛋白病（MGUS；n = 20）及健康对照者（n = 20）血清中游离及与骨保护素（OPG）结合的RANKL（总RANKL，tRANKL），以探讨血清RANKL水平的临床意义。
与对照组（P <.001）或MGUS组（P <.001）相比，MM患者循环血清tRANKL显著升高。此外，冒烟型MM患者的tRANKL水平高于MGUS患者（P =.031），有症状的MM患者高于冒烟型MM患者（P <.001）。血清tRANKL水平随国际分期系统的I至III期升高而升高（P =.004），并与溶骨性骨病变的存在相关（P <.001）。总RANKL是有症状MM患者总生存的预后因素（P =.043）。联合化疗和双膦酸盐治疗3个月后tRANKL水平下降> 50%的患者无进展生存期显著延长。
我们的研究首次表明血清tRANKL反映MM患者的疾病进展、溶骨性骨破坏及预后不良。
