Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival

• Published in: British journal of haematology Vol. 158; no. 6; pp. 727 - 738
• Main Authors: Sanchez, Eric, Li, Mingjie, Kitto, Alex, Li, Jennifer, Wang, Cathy S., Kirk, Dylan T., Yellin, Ori, Nichols, Cydney M., Dreyer, Marissa P., Ahles, Cameryn P., Robinson, Austin, Madden, Erik, Waterman, Gabriel N., Swift, Regina A., Bonavida, Benjamin, Boccia, Ralph, Vescio, Robert A., Crowley, John, Chen, Haiming, Berenson, James R.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.09.2012; Blackwell
• Subjects: Animals; B-cell maturation antigen; B-Cell Maturation Antigen - analysis; Biological and medical sciences; biomarkers; Bone marrow; Bone Marrow - chemistry; Boronic Acids - therapeutic use; Bortezomib; Cell Membrane - chemistry; Cell survival; Culture Media, Conditioned - chemistry; Cyclophosphamide; Cyclophosphamide - therapeutic use; Enzyme-Linked Immunosorbent Assay - methods; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin G - blood; Immunoglobulinopathies; Immunopathology; in vivo; Kaplan-Meier Estimate; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes (mononuclear); Lymphocytes B; Malignancy; Medical sciences; Melphalan; Mice; Mice, SCID; Monoclonal gammopathy; Monoclonal Gammopathy of Undetermined Significance - blood; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - metabolism; Multiple Myeloma - mortality; Multiple Myeloma - pathology; Neoplasm Proteins - analysis; Neoplasm Transplantation; Plasma Cells - chemistry; Pyrazines - therapeutic use; serum; Survival; Tumor Burden; Tumor Cells, Cultured - metabolism; Xenografts; Immunopathology; multiple myeloma; Hematology; xenografts; B-cell maturation antigen; Malignant hemopathy; Transplantation; Heterotransplantation; Myeloma; Survival; In vivo; Treatment; Immunoglobulinopathy; Surgery; Lymphoproliferative syndrome; Animal; Graft; Serum; Cancer
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/j.1365-2141.2012.09241.x

Summary 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.