Institute for Myeloma & Bone Cancer Research, West Hollywood, CA 90069, USA.
Br J Haematol. 2012 Sep;158(6):727-38. doi: 10.1111/j.1365-2141.2012.09241.x. Epub 2012 Jul 18.
Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age-matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients.
尽管 TNFRSF17(也称为 B 细胞成熟抗原(BCMA))在 B 细胞恶性肿瘤的肿瘤细胞上表达,但在血清中未发现。本研究发现,多发性骨髓瘤(MM)患者骨髓单个核细胞培养上清液中的 BCMA 浓度高于健康受试者。在 MM 患者(n=209)、意义未明单克隆丙种球蛋白血症(MGUS)个体(n=23)和年龄匹配的对照组(n=40)的样本中测量了血清 BCMA 水平。在未经治疗的 MM 患者(n=50)的血清中检测到 BCMA,其水平高于 MGUS 患者(P=0·0157)和健康受试者(P<0·0001)。与有反应性疾病的患者(n=79;P=0·0038)相比,进展性疾病患者(n=80)的血清 BCMA 水平更高。在所有 MM 患者中,血清 BCMA 水平高于中位数的患者的总生存期更短(P=0·001)。我们还证明,来自人 MM 异种移植小鼠的血清含有人 BCMA,并且水平与硼替佐米联合美法仑或环磷酰胺治疗后肿瘤体积变化相关。这些结果表明,血清 BCMA 水平可能是监测 MM 患者疾病状态和总生存期的一种新的生物标志物。